Immunogenic cell death (ICD) is a type of stress-induced cancer cell death triggered by certain chemotherapeutic drugs, oncolytic viruses, photodynamic therapy, and radiotherapy, etc. The occurrence of ICD causes the increase of tumor cell immunogenicity and the release of damage-associated molecular patterns (DAMPs), resulting in the activation of CTL-driven immunity. ICD and DAMPs provide new targets for tumor immunotherapy and new venues for improving tumor vaccination strategies. This paper reviews the occurrence of ICD, related molecules in this process, and the mechanism of the antitumor adaptive immune responses.

Inflammation is a pathological process dominated by the defensive response to the stimulation of various damage factors in living tissues with the vascular system. Wild-type p53-induced phosphatase 1 (Wip1) is a PP2C family serine/threonine phosphatase encoded by protein phosphatase, Mg²⁺/Mn²⁺ dependent 1D (PPM1D) gene. Wip1 regulates DNA damage repair and the proliferation, senescence, apoptosis, and autophagy of inflammatory cells through regulation of important signaling molecules including dephosphorylation of p38 MAPK, p53 and ataxia telangiectasia-mutated (ATM) protein. Increasing studies have confirmed that Wip1 plays a key role in regulating many types of inflammatory cells. This review summarizes the structural characteristics of Wip1, the relationship between Wip1 and inflammatory cells, and the role of Wip1 in inflammatory diseases.

Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease as well as an autoimmune disease. Innate immune cell macrophage plays an important role in the pathogenesis of this disease. Yes-associated protein (YAP) is the key protein of Hippo signaling pathway. YAP has been reported to promote proliferation and repair intestinal epithelial cells thus alleviating IBD. However, recent studies have shown that YAP in macrophages aggravates IBD by promoting M1 polarization and that YAP deficiency leads to M2 polarization and IBD alleviation. In recent years, though studies on YAP in macrophages are numerous, the mechanism of YAP regulating polarization in macrophages is yet to be elucidated. Recent studies revealed that YAP in macrophages cooperated with NF-κBp65 to activate NOD-like receptor family pyrin domain-containing protein 3(NLRP3) inflammasome and participated in the pro-inflammatory response of M1 macrophage polarization. This review outlines the current developments of YAP functions in macrophages, including its cooperation with NF-κBp65 to activate NLRP3 inflammasome, the regulation of TAP on M1 polarization and IBD, and the therapeutic prospect of targeting YAP in macrophages.

The establishment of immunotherapy is a major breakthrough in the field of tumor therapy which has changed its landscape. Although immunotherapy is effective in some tumor types, the overall response rate is still low. Therefore, the development of new immunotherapy drugs and treatment strategies is needed. Metabolic reprogramming is a main characteristic of tumors, and the complexity of immuno-metabolism in tumor microenvironment is probably an important factor affecting the efficacy of tumor immunotherapy. Recent studies have proved that targeting immuno-metabolism may relieve immunosuppression, enhance anti-tumor immunity, improve the efficacy of current tumor immunotherapy, and even overcome drug resistance. This article reviews the latest progress in tumor immuno-metabolism-targeted therapies, including targeting glucose metabolism, amino acid metabolism, nucleotide metabolism, and lipid metabolism. This review will provide ideas for developing new targets for immuno-metabolism-targeted therapies.

Mesenchymal stromal cell (MSC) has immunosuppressive properties, and may inhibit inflammatory and autoimmune diseases by regulating various immune cell responses. T cells recognize a variety of pathogens and tumor cells, mediate immune responses, and maintain immune memory and self-tolerance. Meanwhile, T cells are also a major driver of various inflammatory and autoimmune diseases. Different subsets of T cells play different roles in the immune responses. MSC establishes direct or indirect contact with T cells through surface molecules and secretion of soluble factors and produces inhibitory or promotive effects after the interaction. On one hand, MSC mediates the inhibition of T cell proliferation to achieve immunosuppressive effects. On the other hand, MSC corrects the balance between pro-inflammatory factors (such as IFN-γ and TNF-α) and anti-inflammatory factors (such as IL-10) by regulating the differentiation of various T cell subsets. This article reviews the mechanisms by which MSC regulates the differentiation of various T cell subsets.

Single-cell transcriptome atlas of enteroendocrine cells (EEC) in colorectal cancer (CRC) was obtained from large-scale single-cell RNA sequencing (scRNA-seq) datum. Differential expression, function, and pseudotime analysis of EEC scRNA-seq datum suggest that EEC development is related to hormone synthesis/secretion function deficiencies in tumor microenvironment. Analysis of bulk RNA sequencing datum, follow-up information, and drug testing datum from The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) datum of CRC reveal that the biomarker glucagon (GCG) has a positive impact on the survival of CRC patients. The potential application value of GCG gene in the treatment of CRC was explored by means of datum from tumor cell line drug tests. The results of this study provide new insights for the treatment of CRC.

This work aims to develop new treatments for CD3⁺ T cell malignancies. For this purpose, the CD3-targeting monoclonal antibody orthoclone OKT3 (OKT3) was conjugated to the cytotoxic drug monomethyl auristatin E (MMAE) through protease cleavable valine-citrulline (vc) linker to generate an antibody-drug conjugate OKT3-vcMMAE. The molecular weight of OKT3-vcMMAE was verified by SDS-PAGE, and the binding ability to CD3⁺ tumor T cell line was verified by flow cytometry. The in vitro cytotoxic activity of OKT3-vcMMAE was verified by CCK-8, and its capacity to stimulate T cells to release cytokines was tested by the cytometric bead array (CBA). To test the in vivo antitumor efficacy, mice inoculated with T-cell tumor cell lines were treated with OKT3-vcMMAE and tumor burden was measured by bioluminescence imaging. The results showed that OKT3 and OKT3-vcMMAE had a similar affinity to Jurkat cells, with half maximal effective concentration (EC50) of 0.36 and 0.34 μg/mL, respectively. In vitro antitumor experiments revealed that compared to that of the OKT3 group, the viabilities of Jurkat cells in the 1, 10, and 50 μg/mL of OKT3-vcMMAE-treatment groups were significantly decreased (P<0.001). Compared to that of the OKT3 group, the viabilities of HuT78 cells with 10 and 50 μg/mL of OKT3-vcMMAE treatment were significantly decreased (P<0.01). IFN-γ production of primary T cells upon 10 μg/mL of OKT3-vcMMAE treatment was significantly decreased compared to cells treated with OKT3 (P<0.01). In addition, in vivo antitumor experiments showed that compared to that of the PBS control group, the tumor burden of mice in the OKT3-vcMMAE group was significantly reduced on day 13 (P<0.01). This study suggests that the antibody-drug conjugate OKT3-vcMMAE may be a potential treatment for CD3⁺ T cell malignancies, thus providing new insights for the development of anti-T-cell-malignancy drugs.

This study aimed to investigate the clinical prognostic value of cyclin-dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC) and its effect on the malignant biological behavior of HCC cell lines by analyzing The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases and in vitro cell experiments. CDK4 mRNA expression and clinical survival datum of 371 HCC tumor samples and 50 non-tumor (non HCC) samples were downloaded from the TCGA database, and 225 tumor samples and 220 non-tumor (non HCC) tissue samples were downloaded from the GEO database. The relationship between CDK4 level and HCC clinical prognosis was analyzed by Kaplan-Meier method. The CDK4 expression was knocked down by siRNA, and the mRNA and protein levels were measured by qPCR and Western blotting, respectively. The effect of CDK4 knock-down on the biological behaviors of HCC tumor cell lines such as proliferation, invasion, metastasis, cell apoptosis and cell cycle were examined by in vitro cell-culture experiments. The bioinformatic analysis of TCGA and GEO (GSE14520) datum showed that CDK4 expression in HCC tumor samples was significantly higher than that in non-tumor tissues (all P＜0.01), and high expression predicted a poor prognosis (all P＜0.05). In vitro  cell function experiments showed that after knocking down CDK4 in Hep3B and Huh-7 HCC cell lines, the proliferation, invasion, and metastasis potential of si-CDK4 cells were significantly increased compared to those of the si-Control group (all P＜0.05). The apoptosis and the cell cycle  arrest were also inhibited (both  P＜0.05). In summary, high CDK4 expression predicts poor prognosis. However, inhibition of CDK4 promoted the malignant behavior of HCC cells, so CDK4 blockade may not be used as a single target to inhibit the proliferation of HCC. More investigations need to be carried out to assess the potential of CDK4 as a combined therapeutic target.

Runt related transcription factor (RUNX) is the main regulator during embryonic development and is essential for the development of all hematopoietic lineages.  Mutation of RUNX is associated with a variety of diseases. The RUNX transcription factor family consists of Runx1, Runx2, and Runx3. The RUNX protein participates in the formation of the adaptive immune system by regulating the development and differentiation of CD4⁺ and CD8⁺ T cells. This article mainly reviews the regulatory mechanisms of RUNX family members in T cell development.

This study aims to verify the regulation of miR-9-5p on the chondrocyte apoptosis by targeting the silent information regulator factor 2-related enzyme 1 (SIRT1) in osteoarthritis（OA）and  explore the related mechanisms. Primary chondrocytes from mice were isolated and cultured, and the cellular OA model was established by IL-1β-induction. An OA mouse model was also established. Subsequently, the expression of miR-9-5p, Caspase-3 activity, cell activity, and apoptosis  in each group were detected. SIRT1 activity and the above indicators were detected after the targeting of miR-9-5p to SIRT1 was confirmed. The tissue samples of OA mice were stained and analyzed by safranine O-fast green, and the effect of miR-9-5p on chondrocyte apoptosis by inhibiting SIRT1 was verified again in the OA mouse model. The results showed that the expression of miR-9-5p mRNA was significantly increased in OA tissues and IL-1β treated chondrocytes (P<0.001). miR-9-5p inhibited the activity of OA chondrocytes (P<0.001) and promoted apoptosis (P<0.01). miR-9-5p targeted SIRT1 and inhibited the activity of OA chondrocytes (P<0.001) and promoted their apoptosis by inhibiting SIRT1 (P<0.05). The in vitro results were verified in the OA animal model. The study suggests that miR-9-5p may inhibit the activity of OA chondrocytes by targeting SIRT1 and promote the apoptosis of OA chondrocytes to regulate the occurrence and development of OA.

The physical properties of the extracellular matrix (ECM) in lung cancer include solid pressure, interstitial fluid pressure (IFP), and stiffness. This review mainly discusses the roles of these physical properties in the development of lung cancer and their influence on the tumor immune microenvironment. Multiple current studies have shown that fibroblasts respond to solid pressure and play an important role in the occurrence of lung cancer and the cancer immune microenvironment through various signaling pathways. IFP influences the infiltration and invasion of lung cancer through the caveolin-1 and ERK1/2 signaling pathways and may mediate immune tolerance via TGF-β, thus promoting the lung metastasis of breast cancer. There are multiple genes and molecules which may mediate the up-regulation of lung cancer ECM stiffness and positively correlate with lung cancer invasion including Ras association domain family protein1 isoform A and integrin α11β1. In addition, the change of the ECM stiffness also affects the expressions of immune checkpoint proteins on the surface of lung tumor cells, such as PD-L1, indicating that the stiffness may affect lung cancer progression and the cancer immune microenvironment. The understanding of solid pressure, IFP, and stiffness may further elucidate the mechanisms of lung cancer development, immunotherapy, and immunotherapy resistance.

Endothelial to mesenchymal transition (EndMT) is a process in which endothelial cells transform into mesenchymal cells in response to various stimuli. EndMT is associated with a variety of diseases including cardiovascular diseases, organ fibrosis, and cancer. EndMT is mainly mediated by multiple inflammatory mediators. This review discusses the current know-ledge of EndMT with inflammatory mediators in the following two sections: (1) Summarization of the main characteristics of EndMT. (2) Outline of the inflammatory cytokines, inflammatory pathways, and inflammatory cells involved in the EndMT processes. Since the EndMT has attracted considerable attention due to its important roles in diseases, this review aims to provide reference to further explore the role of inflammatory mediators in EndMT and to promote the development of EndMT targeting drugs.

Autophagy is a process of degradation of cellular contents that occurs in various types of cells in the human body. Dysregulation of autophagy correlates with many human diseases. Innate immune cells are a crucial line of defense in anti-infection immunity. They eliminate pathogenic microorganisms through direct phagocytosis and releasing of bactericidal substances or they may stimulate adaptive immunity through antigen presentation. Autophagy plays a vital role in the anti-infection immunity of innate immune cells. This review focuses on the regulation of autophagy on the anti-infection immunity of innate immune cells including macrophages, neutrophils, and dendritic cells.

This study aimed to investigate the expression of cathepsin D (Cat D) in osteosarcoma cells and to explore the effect and mechanism of Cat D on the proliferation, apoptosis and invasion of osteosarcoma cell lines MG63 and U2OS. Cat D was knocked down by short hairpin RNA (shRNA)-mediated gene silencing. To this end, the sh-Cat D and negative control (sh-NC) plasmids were constructed and transfected into osteosarcoma cell lines MG63 and U2OS. RT-PCR and Western blotting were used to detect the expression of Cat D in osteosarcoma cells. CCK-8 assay, clone formation assay, and EdU fluorescence staining assays were used to detect cell proliferation activity. Transwell assay was employed to evaluate cell invasion. FACS was used to assess cell apoptosis. Western blotting was used to measure the expression of cell apoptosis-related proteins (Bax and Bcl-2) and the phosphorylation levels of Akt/mTOR signaling pathway-related proteins (Akt and mTOR). Compared to that of the normal human osteoblastic hFOB cells, Cat D expression levels in osteosarcoma cells MG63 and U2OS were significantly higher (all P＜0.001). Compared to sh-NC, Cat D silencing significantly inhibited the proliferation and invasion of MG63 and U2OS cells (all P＜0.001), up-regulated the expression of Bax, down-regulated the expression of Bcl-2 thereby facilitated cell apoptosis (all P＜0.001). Meanwhile, Cat D silencing significantly inhibited the phosphorylation of Akt and mTOR (all P＜0.001). In addition, the impact of Cat D silencing on the apoptosis and invasion was enhanced by Akt/mTOR signaling pathway inhibitor (Wortmannin) and dampened by Akt/mTOR signaling pathway agonist (740 Y-P) (all P＜0.001). In conclusion, Cat D was highly expressed in osteosarcoma cells. Cat D silencing could up-regulate the apoptotic activity and inhibit osteosarcoma cell growth by suppressing the phosphorylation level of Akt/mTOR signaling pathway, suggesting that Cat D may be a potential therapeutic target for osteosarcoma.

The human immune system includes innate immunity and adaptive immunity. Innate immune cells recognize dangerous endogenous and exogenous antigens through PRR. PRR include TLR, NOD-like receptors (NLR) and C-type lectin receptors (CLR), etc. NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome belongs to the NLR family and as the core of inflammatory response, it is closely related to the occurrence and development of many malignant tumors, including multiple hematological tumors. This article reviews the latest research progress on the relationship between NLRP3 inflammasome and lymphoma, leukemia, myelodysplastic syndrome, and multiple myeloma.

Trained immunity refers to the immunological memory exhibited by innate immune cells, which is similar to that of adaptive immune cells. Increasing evidences indicate that trained immunity contributes to the inhibition and even elimination of infections caused by foreign pathogens, including Mycobacterium tuberculosis (M. tuberculosis). Traditional tuberculosis vaccine design focuses on the induction of tuberculosis-specific adaptive immunity. Among them, the emerging concept represented by Bacille Calmette-Guérin (BCG)-induced trained immunity provides  new strategies for the design and development of tuberculosis vaccines. This review summarizes the role of trained immunity in M. tuberculosis infection as well as the possibilities and challenges of targeting trained immunity in future tuberculosis vaccine design.

This study aims to improve the accuracy of multi-microsphere flow immunofluorescence assay in the clinical detection of cytokines. To this end, peripheral blood samples from patients were collected, and the effects of serum, plasma, different storage conditions, and interfering substances on the results of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) were analyzed. The results showed that the levels of IL-6 and IL-8 in the serum sample were significantly higher than those in the plasma sample (P<0.05), while the levels of the other cytokines including IFN-α, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, and IL-17 showed no difference between serum and plasma (P>0.05). The levels of some cytokines changed slightly when EDTA-K2 was used as anticoagulation in whole blood samples stored at 4 ℃ for 24 h. However, the cytokines levels in plasma decreased significantly after being stored at 4 ℃ for 48 h (P<0.05). The detection signal and analysis results of abnormal samples (missing microspheres or abnormally enhanced fluorescence signal) were returned to normal after pretreatment with mouse immunoglobulin. The study indicates that the cytokine levels in EDTA-K2 anticoagulant plasma samples or samples stored at 4 ℃ within 24 h are more stable than those in whole blood samples. In addition, pretreatment with mouse immunoglobulin is an effective method to solve the loss of microspheres or abnormal fluorescence signals of microspheres. 

In this study, a type of fluorescence immuno-chromatography reagent card that may be applied for the quick quantitative detection of IL-6 was developed. A recombinant human IL-6 protein was expressed in E. coli as a standard for the IL-6 testing  card. First, the human IL-6 gene was cloned to the expression vector pET30a after codon optimization, which was subsequently transformed into E. coli BL21 competent cells for inducible expression. By isopropylthio-β-D-galactoside (IPTG) induction, the soluble form of IL-6 protein was obtained. After  Ni2+ column affinity chromatography purification and ultrafiltration, the IL-6 protein standard sample was acquired. The fluorescence immuno-chromatography reagent card was prepared by time-resolved fluorescent microspheres, based on the fluorescence immuno-chromatography technology and sandwich ELISA. By property evaluation, the blank limit was 5.2 pg/mL. The coefficient of variation was between 7.34% to 11.11%, exhibiting good repeatability. The recovery rate was between 96.3% and 107.2%. The reagent card showed good stability after six weeks storage at 37 ℃. There was no cross-reaction with common competitors, with the reference value ranging from 0 to 9.0 pg/mL. The outcome of our method on the clinical samples testing was comparable to that of the electrochemi-luminescence immunoassay (ECLIA) (r = 0.965). In conclusion, the recombinant IL-6 protein prepared in this study is of high purity and concentration, which is qualified as kit testing standard. And the developed reagent card is convenient to use and could meet the needs of clinical applications.

Neutrophil extracellular trap (NET) discovered seventeen years ago has an essential role in anti-infection immunity. NETs are extracellular DNA fibers containing histones and cytoplasmic granular proteins. They were believed to form a natural immune barrier against pathogens invasion by trapping pathogens, degrading bacterial virulence factors, and killing bacteria. NETs also have effects against other pathogens including fungi, viruses, and parasites. However, the over-formation of NET can lead to a variety of diseases, and NET-associated proteins may also damage tissue. This review concentrates on the role of NET in defending pathogen infections, the immune escape of pathogens from NET, and the dual functions of NET.

This study aims to develop a method to efficiently and stably induce the differentiation and expansion of human myeloid-derived suppressor cells (MDSC) in vitro and provide new experimental technology for the study of the function and mechanism of human MDSC. For this purpose, PBMC of healthy volunteers were isolated with Ficoll density gradient centrifugation. Next, monocytes were separated by anchoring technique. PBMC or monocytes were stimulated with GM-CSF and IL-6 (10, 20, 40, 80 ng/mL each) for 4, 7, 14, and 21 days before co-culturing with PBMC for 3 days. The proliferation of CD33⁺ MDSC and T cells and the proportion of CD3⁺IFN-γ⁺ T cells were detected by FACS. The results showed that the PBMC or monocytes were induced to differentiate to less CD33⁺MDSC by conventional methods. However, by improved methods, the monocytes cultured with GM-CSF and IL-6 (each 80 ng/mL) for 14 days (refreshing the culture solution every 4-5 days) were induced to differentiate more efficiently into a higher proportion of CD33⁺MDSC, which showed significant inhibition of T cell proliferation and IFN-γ secretion. This study suggests that with the improved method, the monocytes are efficiently induced to differentiate into CD33⁺ MDSC, which has significant suppressive function.

As a type of APC, macrophages play an important role in both innate and adaptive immune responses, involving in phagocytosis, tissue remodeling and repair, angiogenesis, and immune tolerance. During pregnancy, macrophages are broadly located at the maternal-fetal interface and own diverse functions and plasticity. Preeclampsia (PE) is a serious complication of pregnancy whose pathogenesis is yet to be elucidated. In recent years, the role of macrophages at the maternal-fetal interface in PE has attracted increasing attention. Starting from the classification and regulation of maternal-fetal interface macrophages, this review focuses on their role in various pathologic processes of PE, including insufficient trophoblastic invasion, uterus spiral arterial remodeling disorder, the immune imbalance of maternal-fetal interface, vasoendothelial damage and metabolic   reprogramming.

The aim of this study is to verify the predictive value of anti-neutrophil cytoplasmic antibodies (ANCA) in early renal injury in children with Henoch-Schonlein purpura（HSP）. Children with HSP (n=2 152) were selected as HSP group which was further divided into purpura type HSP group (n=1 977) and nephritis type HSP group (n=175) based on the presence of renal injury. Meanwhile, 76 healthy children were selected as healthy control. The ANCA positive rates were analyzed, as well as the reciprocal relationship between ANCA positivity and immune function, including immunoglobulin (IgG, IgM, IgA), complement (C3, C4), and cellular immunity (the percentages of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD3^－CD16⁺CD56⁺, CD3^－CD19⁺ cell). Urinary microalbumin (MA), urinary IgG, and urine alpha 1-microglobulin (α1-MG) were measured to explore the association between ANCA and renal injury. The results showed that 176 out of 2 152 children with HSP were ANCA positive (8.18%) whereas all healthy children were ANCA negative. The levels of IgG, IgM, IgA, C3, C4, and the percentage of CD3^－CD19⁺ cells in HSP children with positive ANCA were significantly higher than those in the healthy control group (P<0.01) whereas the percentages of CD3⁺, CD3⁺CD4⁺, CD3^－CD16⁺CD56⁺ cells were significantly decreased than those in the healthy control group (P<0.01). There was no significant difference in the percentage of CD3⁺CD8⁺ cells between the two groups (P>0.05). And there was no significant difference in all the indices between purpura and nephritis type HSP (P>0.05). The levels of urinary MA, urinary IgG, and urine α1-MG in ANCA-positive HSP children were significantly higher than those in ANCA-negative HSP children (P<0.05). In conclusion, positive ANCA is associated with enhanced humoral immunity as well as decreased cellular immunity in children with HSP. ANCA may be a predictive biological indicator for early renal injury in children with HSP.

This study aims to investigate the expression of PD-L1 in human colorectal cancer (CRC) and its correlation with clinicopathological characteristics. PD-L1 expression was measured by immunohistochemistry of CRC patients and analyzed to reveal its relationship with histological tumor grade and metastasis. PD-L1 expressions in CRC tissue and para-cancerous tissue were measured by ELISA. The results showed that PD-L1 expression was significantly correlated with histological tumor grade. PD-L1 expression increased with the decreasing of tumor differentiation levels from high to low (P<0.01). However, there was no apparent correlation between PD-L1 expression and metastasis condition (P>0.05). The expression of PD-L1 in CRC tissue was significantly higher than that in para-cancerous tissue (P<0.001). The study suggests that PD-L1 expression is higher in CRC tissue, compared to that in para-cancerous tissue, and PD-L1 expression is significantly associated with histological tumor grade, making it a potential indicator to assess the clinical prognosis of CRC patients. 

Since the interaction between intestinal microbes and the immune system  was discovered, the key role of intestinal flora in rheumatic diseases has been recognized and studied by ever-increasing scholars, and has become a research hotspot. Intestinal flora not only participate in the organism nutrient absorption, material metabolism and energy conversion, but also play an important role in the development and maturation of the immune system, the differentiation of immune cells and the regulation of immune mediators. The pathogenesis of ankylosing spondylitis (AS) is not fully understood but it is may be a genetic disease related to the HLA-B27. The inflammation of the sacroiliac joint and spinal attachment point caused by autoimmune abnormalities is the main pathological feature. The latest researches have shown that the intestinal flora are closely related to  HLA-B27, the development and regulation of the immune system, IL-23/Th17 axis and other factors that affect the pathogenesis of AS. Therefore, this article reviews the relationship between the intestinal flora, the immune system and AS, and provides a new perspective for the research and clinical application on rheumatic immune diseases. 

The study aims to explore the effects and mechanism of miR-30b-5p on the proliferation and apoptosis of lung adenocarcinoma cells by targeting helicase lymphoid-specific (HELLS). To this end, the expressions of miR-30b-5p and HELLS in lung adenocarcinoma tissues and their relationship with clinical phenotypes were analyzed by bioinformatics. Next, A549 and Calu-3 cells cultured in vitro were divided into the miR-NC group (transfected with miR-NC), miR-30b-5p group (transfected with miR-30b-5p), and miR-30b-5p+HELLS group (transfected with miR-30b-5p and HELLS). The mRNA expressions of miR-30b-5p and HELLS in each group were detected by RT-PCR. The expressions of nucleoprotein antigen Ki67 and HELLS proteins in each group were detected by Western blotting. The cell proliferation was detected by CCK-8. The cell survival ability in each group was detected by colony formation assay. The cell cycle and apoptosis rate in each group were detected by FACS. The targeted relationship between miR-30b-5p and HELLS was verified by dual-luciferase assay. Then the xenograft models of nude mice with lung adenocarcinoma were established and divided into miR-NC group and miR-30b-5p group. The volume and weight of tumors were measured. The expression of Ki67 protein in xenograft tumors was analyzed by immunohistochemistry. The results showed that based on GEO2R and TCGA, the expression of miR-30b-5p in lung adenocarcinoma tissues was down-regulated, and correlated with survival period, N staging, recurrence, and prognosis (P<0.05). The expression of HELLS in lung adenocarcinoma tissues was significantly higher than that in para-cancerous tissues (P<0.05) and correlated with the staging of TNM, tumor grading, prognosis, and survival period (P<0.05). Compared to the miR-NC group, the expression level of miR-30b-5p, the number of cells in G0/G1 phase, and the apoptosis rate  in A549 and Calu-3 cells were all significantly increased in the miR-30b-5p group (P<0.05), while the cells activity, number of clone cells, number of cells in S phase, levels of HELLS mRNA, Ki67, and HELLS protein were significantly decreased (P<0.05). Compared to the miR-30b-5p group, the number of cells in G0/G1 phase and apoptosis rate were significantly decreased in the miR-30b-5p+HELLS group (P<0.05), while the cells activity, number of clone cells, number of cells in S phase, levels of Ki67 and HELLS proteins were significantly increased (P<0.05). The dual-luciferase assay confirmed that miR-30b-5p could target HELLS. Compared to the miR-NC group, the volume and weight of xenograft tumors, and the cellular Ki67 level were significantly decreased in the miR-30b-5p group (P<0.05). The results conclude that miR-30b-5p inhibits the proliferation and induces apoptosis of lung adenocarcinoma cells by negatively regulating the expression of HELLS.

The bone marrow microenvironment (BMM) plays an important role in the development of acute myeloid leukemia (AML). Multiple studies have shown that T cells can maintain immune homeostasis and promote the differentiation balance of hematopoietic stem cells in normal BMM. However, the immune homeostasis of T cells in BMM is disrupted and unbalanced in AML, suggesting that the imbalanced BMM T cell state may be involved in the development of AML. The characteristics of BMM T cell homeostasis imbalance and the value of the imbalance in the prognosis and treatment of AML patients have not been fully understood. This review outlines the role of T cells in the normal bone marrow and the potential value of BMM T cell immune homeostasis in prognosis prediction and treatment of AML patients.

The purpose of this study was to investigate the effect of miR-let-7a on the proliferation and inflammatory response of human mesangial cell (HMC) induced by LPS and the mechanism by which miR-let-7a acts in regulating PI3K/Akt signaling pathway.  To this end, HMCs were treated with 0.1 μg/mL LPS in vitro.  The cell viability was measured by CCK-8 assay; the expressions of proliferating cell nuclear antigen (PCNA), apoptosis-related protein BAX, and signaling pathway proteins PI3K and p-Akt were detected by Western blotting; the mRNA levels of miR-let-7a and inflammatory factors TNF-α, IL-1β, IL-6 and collagen Ⅳ in HMC were measured by qPCR.  The expression of miR-let-7a in HMC was motified by transfecting either miR-let-7a mimic or inhibitor and the PI3K/Akt signaling pathway was blocked by using the inhibitor LY294002.  The effects of the above treatments on HMC proliferation, inflammatory response, and the activation of  PI3K/Akt signaling pathway were examined.  The results showed that LPS stimulation induced the proliferation and inflammatory response of HMC, inhibited the expression of miR-let-7a (all P＜0.05), and activated the PI3K/Akt signaling pathway (all P＜0.01). Compared to LPS-treated group, over-expression of miR-let-7a down-regulated LPS-induced HMC proliferation and inflammatory response and inhibited the activation of the PI3K/Akt signaling pathway (all P＜0.05). On the other hand, down-regulation of miR-let-7a promoted cell proliferation, inflammatory response, and PI3K/Akt signaling pathway activation induced by LPS stimulation (all P＜0.05). Blocking the PI3K/Akt signaling pathway also inhibited HMC viability and the production of inflammatory factors (all P＜0.05). In conclusion, in LPS-stimulated HMC, miR-let-7a inhibits the proliferation and inflammatory response of HMC by regulating the PI3K/Akt signaling pathway.

The goal of this study is to investigate the effect of dimethyl fumarate (DMF) on the JAK2/STAT3 signaling pathway and its anti-oxidative stress ability on chondrocyte mitochondria and inflammatory response in order to provide a theoretical basis for DMF as a therapeutic drug for  osteoarthritis (OA). For this purpose, rat chondrocytes were induced by LPS to establish an OA model in vitro. Twenty-seven 4-week-old male SD rats were selected and divided into three groups: control group, model group (LPS), and treatment group (LPS+DMF). Chondrocytes were collected and the expressions of inflammatory factors IL-1β, IL-6, and TNF-α were measured by ELISA. The mRNA expressions of JAK2, STAT3, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 1 (COX1) were detected by qRT-PCR. And the protein levels of p-JAK2, JAK2, p-STAT3, STAT3, SDHA, and COX1 were detected by Western blotting. The results showed that, compared to those of the control group, the expression of IL-1β, IL-6, and TNF-α was significantly higher in the model group (all P＜0.05). In contrast, the mRNA levels of JAK2, STAT3, SDHA, and COX1 mRNA were decreased significantly (all P＜0.01). The phosphorylation of JAK2 and STAT3 was decreased, along with the protein expressions of SDHA, and COX1 (all P＜0.05). In the treatment group, when compared to those of the model group, the concentrations of IL-1β, IL-6, and TNF-α were reduced significantly (all P＜0.05). The mRNA expressions of JAK2, STAT3, and SDHA were increased significantly (all P＜0.01). The phosphorylation of JAK2 and STAT3 were increased significantly, and the protein expressions of SDHA and COX1 were also increased significantly (all P＜0.05). In conclusion, JAK2/STAT3 signaling pathway is closely related to the occurrence and development of OA. DMF may inhibit OA by reducing the expression of inflammatory factors and activating the JAK2/STAT3 signaling pathway, thus elevates the mitochondrial antioxidative capacity. DMF has a broad and further application prospect in the treatment of OA.

There are two forms of thyroid hormone (TH): 3, 5, 3'-triiodothyronine (T3) and 3, 5, 3', 5'-tetraiodothyronine (T4, or termed thyroxine). They act on almost all tissues of the body, with a wide range of biological processes including metabolism, growth, and development. Recent studies have brought attention to their regulation on innate immune cells. Thyroxine has been shown to affect the M1 and M2 states of macrophages. In addition, macrophages express type 2 deiodinase (D2), which can regulate different molecular forms of intracellular TH. The abnormal thyroid function also affects the biological activity of macrophages such as their anti-inflammatory activity. In addition, hypothyroidism aggravates atherosclerosis. Although there is no sufficient evidence to prove the clinical correlation between thyroid hormones and macrophages, thyroid hormone level may be used as a factor to predict clinical susceptibility to infections, tumors, and autoimmune diseases. 

Kidney stone is a disease of high incidence and recurrence rate and has become an obstacle in urology. Recent studies have demonstrated the role macrophages play in the development of calcium oxalate nephrolithiasis. Macrophages regulate the occurrence and development of calcium oxalate nephrolithiasis via various mechanisms, such as polarization into different subtypes, secretion of cytokines, crystals phagocytosis, and activation of signal transduction pathways. This review discusses the research progress on the mechanism of macrophages in calcium oxalate nephrolithiasis.

This research proposes to determine the immune function of the body in the disease state by analyzing the correlation between the expressions of CD8⁺T cell molecular markers and cytokines in children with viral pneumonia. FACS was used to detect the CD8⁺CD38⁺, CD8⁺CD28⁺, CD8⁺PD-1⁺, CD8⁺T cell immunoglobulin and mucin domain 3 (Tim-3)⁺T cells percentage in 65 children with viral pneumonia and those in 49 healthy children and cytometric bead array(CBA) was used to measure the levels of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ. The correlations between CD8⁺T cells with different surface markers and cytokines were analyzed. The results showed that compared to those in the control group, the proportion of CD8⁺CD38⁺, CD8⁺CD28⁺, CD8⁺PD-1⁺, and CD8⁺Tim-3⁺T cells in the patient group was increased（P＜0.05）. The levels of IL-2, IL-4, IL-6, TNF-α, and IFN-γ were increased（P＜0.05）, and the level of IL-10 was decreased（P＜0.05）. The percentage of CD8⁺CD38⁺ T cells was positively correlated with the levels of IL-2, IL-4, IL-6, IL-17A, and IFN-γ（P＜0.05）. The percentage of CD8⁺CD28⁺ T cells was positively correlated with the levels of IL-10 and IFN-γ（P＜0.05）, and negatively correlated with the levels of IL-2, IL-4, and IL-6（P＜0.05）. The percentage of CD8⁺PD-1⁺ T cells was positively correlated with IL-4, IL-6, IL-17A, TNF-α, and IFN-γ（P＜0.05）. The percentage of CD8⁺Tim-3⁺ T cells was positively correlated with IL-2, IL-4, IL-6, TNF-α, and IFN-γ（P＜0.05）. There were differences among different virus infection groups. The research suggests that immune abnormalities are involved in the development of viral pneumonia in children. The immune status of the children can be assessed by the detection of relevant immune indicators.

The aim of this study is to investigate the protective effect and the underlying mechanism of bilirubin on lung tissue damage  via macrophage efferocytosis in smoking-exposed rats. Six-week-old healthy male Wistar rats were randomly divided into six groups of ten. The rat smoking model was established by twelve weeks＇ smoking. A smoking withdrawal model was established by twelve weeks of smoking followed by four weeks of withdrawal. Exogenous bilirubin was given in treatment groups before daily smoking exposure. Specimens were retained for pulmonary histology and histopathological analysis. ELISA was used for the detection of cytokine levels in bronchoalveolar lavage fluid (BALF) and FACS for the percentage of macrophages with efferocytosis. The results showed that after twelve weeks of smoking exposure, the emphysema model was successfully established, and the cigarette smoke exposure significantly increased the infiltration of inflammatory cells, the levels of inflammatory cytokines, and lung tissue damage (all P＜0.05). In addition, smoking also affected macrophage polarization towards the M1 type. Smoking also affected macrophage efferocytosis  (all P＜0.05). The inflammatory response and damage of lung tissue after four weeks of smoking withdrawal were moderately alleviated (all P＜0.05), but still existed. Exogenous bilirubin intervention reduced the infiltration of inflammatory cells, the secretions of partial inflammatory cytokines, and relieved lung tissue damage (all P＜0.05), which might correlate to its regulation on the macrophage polarization state and efferocytosis (all P＜0.05). In conclusion, bilirubin may alleviate lung tissue damage caused by cigarette smoke exposure via multiple mechanisms such as anti-inflammatory, antioxidant, and immunomodulatory. The discovery of the effect of bilirubin on the polarization state and efferocytosis of macrophages is complementary to the known functions of bilirubin and provides the theoretical basis and new ideas for the application of bilirubin to treat cigarette smoke-related inflammatory diseases.

IL-22 is a member of the IL-10 cytokine family and plays important roles in inflammatory regulation, barrier defense, homeostasis, and tissue repair. Recent studies have shown that IL-22 not only improves liver fibrosis induced by various factors but also has protective and therapeutic effects on various benign liver diseases such as viral hepatitis, autoimmune hepatitis, alcoholic hepatitis, and non-alcoholic fatty liver disease. However, IL-22 has been shown to promote the proliferation and survival of tumor cells in primary liver cancer. This review summarizes the recent research progress of IL-22 in liver diseases.

This study proposes to investigate the association between single nucleotide polymorphism (SNP) of B cell activating factor belonging to the TNF family (BAFF) and BAFF-receptor (BAFF-R) and graft renal function. To this end, anticoagulant peripheral blood and serum were collected from 310 randomly selected following-up renal transplantation recipients and 51 healthy controls. Five BAFF/BAFF-R SNPs were selected and genotyped by Taqman qRT-PCR. The results of the Hardy-Weinberg equilibrium test showed that the distribution of genotypes was representative of the population. Based on the critical value of the estimated glomerular filtration rate (eGFR) of 90 mL/ (min·1.73 m²), the recipients were divided into eGFR normal and eGFR abnormal groups. Logistic regression analysis showed that in the heterozygote genetic model, BAFF rs9514828 CT genotype carriers had a significantly higher incidence of abnormal graft kidney function than other genotype carriers (OR=1.597, 95%CI 1.012-2.519, P<0.05) whereas it had no significant correlation with serum soluble BAFF（sBAFF）level or positive rate of panel reactive antibody（PRA）. The other four SNP genotypes showed no significant difference between groups. Haploview 4.0 software analysis showed that there was a strong linkage disequilibrium between rs16972194, rs9514828, and rs16972197 in BAFF. Haploid analysis showed that haploid “GCG” carriers had a significantly higher chance of normal graft function (OR=0.381, 95%CI 0.156-0.931, P<0.05). Altogether, the results suggest that for kidney transplant recipients, BAFF rs9514828 CT genotype may be a risk factor for reduced graft function, and the haploid GCG may be a protective factor in favor of normal graft function.

The purpose of this study is to investigate the effect of γ-secretase inhibitor in regulating γδT17 cells by blocking the Notch1 signaling pathway on thyroid autoimmune injury in experimental autoimmune thyroiditis (EAT) mice. Thirty female C57BL/6 mice were randomly divided into normal control (NC) group (n=10), EAT-A group (treated with porcine thyroid immunoglobulin ［pTg］, n=10), and EAT-B group (treated with N-［N-3,5-difluorophenacetyl-L-alanyl］-S-phenylglycine t-butyl ester ［DAPT］ before pTg, n=10). H-E staining, ELISA, flow cytometry, and qRT-PCR were used to assess the degree of thyroiditis and detect the expressions of γδT17 cells and their effector cytokine IL-17A, the main components of Notch1 signaling pathway, respectively. The results showed that the serum titre of thyroglobulin antibody (TgAb), the level of IL-17A, the proportion of γδT17 cells, and the Notch1, hairy and enhancer of split 1 (Hes1), IL-17A mRNA expressions in the EAT-A group were all significantly higher compared to those in the NC group (P<0.01). In contrast, in the EAT-B group, the above indexes were all significantly decreased upon DAPT treatment (P<0.01), accompanied by reduced lymphocyte infiltration in the thyroid. Additionally, the proportion of γδT17 cell  in EAT mice was positively correlated with the serum concentrations of TgAb and IL-17A (r=0.598, 0.497, P<0.05). Therefore, the results suggest that γ-secretase inhibitor can reduce thyroid autoimmune injury by blocking the Notch1 signaling pathway to downregulate the γδT17 cells in EAT mice.

Vedolizumab is a humanized anti-integrin α4β7 monoclonal antibody believed to exhibit high intestinal specificity. Its impact on the immune system of patients with inflammatory bowel disease (IBD) is reported to be mostly restricted to the intestine. In a humanized mouse model, vedolizumab blocks T-cell trafficking to inflamed intestinal tissue. Therefore, preventing the transport of T cells to the gut is thought to be the main mechanism of vedolizumab in reducing intestinal inflammation. However, with the wide application of vedolizumab, its effects on systems other than the gut have been reported. In addition, its target cells are found not limited to T cells. Vedolizumab also acts on innate immune cells as well as B cells in the gut of IBD patients. Besides, vedolizumab may also be used to treat extra-intestinal manifestation (EIM) accompanied with enteral disease activity, such as peripheral arthritis and erythema nodosum. This review summarizes the effects of vedolizumab on different systems in IBD patients to help fully understand the mechanism of action of vedolizumab.

DC, as the most important APC in the human body, is an essential factor in the immune responses to allergic rhinitis. In recent years, the research on the correlation between DC and allergic rhinitis has developed rapidly. DC is the "bridge" between innate and adaptive immunity because they interact with various co-stimulatory molecules, adhesive molecules, T cells, and B cells to regulate the immune responses of allergic rhinitis. This article reviews the role of DC in allergic rhinitis, their interaction with multiple immune molecules on allergic rhinitis, their regulatory effect on allergic rhinitis in the nasal mucosa, and DC-related treatments of allergic rhinitis.

In this paper, the relationship between inflammasome activation and histopathology and salivary flow rates in mice with Sjogren's syndrome (SS) was studied to elucidate the role of inflammasome activation in SS. Female non-obese diabetic (NOD) mice of 12-week-old were selected as SS model mice while female Institute of Cancer Research (ICR) mice of the same age were used as controls. Firstly, the salivary flow rates, the histopathology of submandibular glands and lungs, and the levels of inflammasomes were measured in both the NOD and control groups. The NOD mice were treated with LPS to activate or with BAY11-7082 to inhibit the inflammasomes pathways. Then, the salivary flow rates, histopathology of submandibular glands and lungs, and the levels of inflammasomes were analyzed. The results showed that the salivary flow rates decreased significantly (P＜0.05), the number of lymphocytic infiltration foci in the lungs and submandibular glands increased significantly, and the activation of inflammasome pathways  increased significantly in NOD mice compared to ICR mice (all P＜0.05). After the activation of inflammasomes by LPS, the salivary flow rates decreased significantly (P＜0.001), and the number and area of lymphocytic infiltration foci in submandibular glands and lungs increased significantly in NOD mice. The serum levels of IL-1β and IL-18 were markedly increased in LPS-treated NOD mice than in PBS-treated NOD mice (both P＜0.05). After inhibition of inflammasomes by BAY11-7082, the salivary flow rates increased significantly (P＜0.05), and the number and area of lymphocytic infiltration foci in submandibular glands and lungs decreased significantly in NOD mice. The serum levels of IL-1β and IL-18 were markedly decreased in NOD mice with BAY11-7082 treatment than those of controls (both P＜0.05). These findings suggest that inflammasome activation is involved in the pathogenesis of SS, and targeting inflammasome activation may be a potential strategy for SS treatment. 

This study aims to explore the molecular mechanism of brain-derived neurotrophic factor (BDNF) on airway hyperresponsiveness in asthmatic mice through tyrosine kinase receptor B (TrkB)-Ca²⁺ signaling. The asthmatic mouse model was established by ovalbumin (OVA). Broncho alveolar lavage fluid (BALF) was obtained to perform cell count and differential count. H-E staining was used to observe the inflammatory changes in lung tissue and measure airway wall thickness. ELISA was used to detect the levels of BDNF in BALF, serum, and lung tissue. The expressions of BDNF and TrkB protein and mRNA in lung tissue were detected by immunohistochemistry, Western blotting, and qRT-PCR. BDNF small interfering RNA (si-BDNF) and protein kinase C (PKC) small interfering RNA (si-PKC) were transfected into pulmonary artery smooth muscle cells isolated from mice of the asthma model group to knock down BDNF and PKC expression and the levels of Ca²⁺ in lung tissue cells were measured by colorimetry. The results showed that compared to those of the control group, the total number of cells, eosinophils, lymphocytes, and neutrophils in BALF of the asthma model group were significantly increased (P<0.05), while the number of monocytes was significantly decreased (P<0.05). There were more inflammatory cells infiltrated in the lung tissue of the asthma model group and the airway wall became thicker (P<0.05). The levels of BDNF in BALF, serum, and lung tissue were significantly increased (P<0.01). The levels of BDNF, TrkB protein, and mRNA were significantly increased (P<0.001). The level of Ca²⁺  in lung tissue cells was up-regulated (P<0.01), but down-regulated after inhibition of BDNF and PKC (P<0.05). In conclusion, BDNF may increase the level of Ca²⁺  and vasoconstriction by activating the downstream PKC signaling pathway, resulting in airway hyperresponsiveness in asthma.