30 November 2022, Volume 42 Issue 6

  

• Select all
  |

• Select
  Regulation of butyrate on STING signaling pathway in bone marrow-derived dendritic cells

  LIU Shuo, LI Yu-ting, LI Hong-hui, CHEN Shao-dan, TAO Ze-hua, JIANG Ya-lan, YU Wan-jun, YAO Xue, SHAO Qi-xiang, XIA Sheng

  2022, 42(6): 457-465.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  To explore the regulation of butyrate (BU) on the stimulator of interferon gene (STING) signaling pathway in bone marrow-derived dendritic cell (BMDC) stimulated by cyclic GMP-AMP (cGAMP), BMDCs were induced and cultured in vitro, and subsequently divided into the control group, BU group, cGAMP group, BU+cGAMP group, poly (deoxyadenylic-deoxythymidylic) (Poly ［dA:dT］)/lip2000 group, and BU+Poly (dA:dT)/lip2000 group. The morphology of BMDCs in each group was observed under a light microscope. The fluorescence intensity of surface markers CD80, CD86, and MHCⅡon BMDCs, and the efficacy of BU and/or cGAMP on CD4⁺T cell priming were analyzed using FACS. The concentration of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in cultured BMDCs were detected by Griess coupling analysis and qPCR, respectively. The mRNA levels and protein concentrations of IFN-β, IL-6, and IL-12 in BMDC culture supernatant were detected using qPCR and ELISA. Western blotting was used to detect the expression of proteins related to the STING signaling pathway, including STING, TANK binding kinase 1 (TBK1), and p-TBK1. The results showed that BU up-regulated the expression of surface markers CD80, CD86, and MHCⅡon BMDCs, but inhibited the STING agonist cGAMP stimulated expression of CD80, CD86, and MHCⅡ. Moreover, BU treatment inhibited the synthesis and secretion of NO, IL-6, and IFN-β in cGAMP-stimulated BMDCs（all with P＜0.05）. BU inhibited CD4⁺T cell proliferation in cGAMP-activated BMDCs but had no obvious effect on the differentiation of naive CD4⁺T cell to Th1. In addition, STING agonist Poly (dA:dT) induced secretion of IFN-β, IL-6, and IL-12 in BMDC was inhibited by BU（all with P＜0.05). Therefore, BU inhibits the expression levels of CD80, CD86 and MHC Ⅱ on cell membrane and the priming ability on CD4⁺T cell proliferation of cGAMP activated BMDC. Moreover, the secretions of NO, IL-6 and IFN-β in these BMDCs were also suppressed. 
• Select
  Construction of P2Y14 knockout mice to explore its regulation of immune response

  LU Bing-lin, QIN Ju-liang, CHE An-ran, QIAN Chun-mei, CEN Yu-rong, DU Bing, WANG Qin

  2022, 42(6): 466-473.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  To explore the roles of purinergic receptor P2Y, G-protein coupled, 14  (P2Y14) in immune and inflammatory responses, CRISPR/Cas9 technology was used to construct P2Y14  knockout (P2Y14  KO) mice. After confirmation of their progeny by PCR and sequencing, the development and immune response of the P2Y14  KO mice were monitored by the following methods: FACS was used to detect mouse thymus and spleen T, B cells and the subgroup percentages; real-time fluorescent quantitative PCR and ELISA were used respectively to detect the mRNA and protein levels of inflammation-related factors in the mouse peritoneal exudative macrophage (PEM) upon LPS stimulation in both the wild type (WT) group and P2Y14  KO group. The results revealed that the P2Y14  KO mice were constructed successfully and compared to WT mice, P2Y14  KO mice showed no significant difference in body weight and the weight and histology of liver, spleen and kidney were also normal. In contrast, the thymus mass (P＜0.01) and the thymus percentages of CD3⁺, CD8⁺T cells increased significantly (P＜0.05 and P＜0.01, respectively) while there was no significant difference in splenic lymphocytes and their subgroups. Upon LPS stimulation, the inflammatory factor IL-6 and the chemokine CCL2 in the P2Y14  KO mice PEM were significantly reduced at both mRNA and protein levels compared to those of WT mice (P＜0.01 and P＜0.001, respectively). Altogether, this study successfully constructed the P2Y14  KO mice and showed that the deletion of P2Y14  promoted the differentiation and development of T cells in the thymus, while significantly reduced the secretion of macrophage inflammatory factors in immune response to LPS.
• Select
  The mutation of CD28 exhibits improved safety in CAR T immunotherapy

  ZHANG Ting-ting, WANG Tian, YOU Feng-tao, LI Zi-xuan, TIAN Shuai-yu, ZHANG Kai-lu, SHENG Bin-jie, WU Hai, AN Gang-li, MENG Hui-min, WANG Min, WANG Xing-bing, YANG Lin

  2022, 42(6): 474-481.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The goal of this study is to improve the potential cytokine storm problem after CD19-targeted chimeric antigen receptor (CAR) T cell therapy and increase the safety of the clinical application. To this end, the YMNM and PYAP fragments in the CD28 costimulatory domain were double-mutated. The CD19-CAR containing either the CD28 domain (19-CD28) or the CD28 mutation domain (19-CD28M) were constructed and a lentiviral system was used to generate the CD19-CAR T cells and CD19-CAR Jurkat cells. The CD19-CAR Jurkat cells were then incubated with tumor cells to verify the specific activation of CD19-CAR on Jurkat cells. Then the cytotoxicity and cytokine release of CD19-CAR T cells after incubation with target cells were evaluated. The results showed that compared with control, the 19-CD28-CAR Jurkat cells and 19-CD28M-CAR Jurkat cells incubated with Raji (CD19⁺) cells showed an increase of CD69 expression by more than 60%, and CD25 by about 10%. The apoptotic rates of Raji (CD19⁺) cells induced by 19-CD28-CAR T cells and 19-CD28M-CAR T cells were about 15%, 25%, and 40% higher than those of the control group at the ratio of effect to the target of 0.5∶1, 1∶1 and 5∶1, respectively. The killing effect reached saturation at the ratio of effect to the target of 5∶1. Meanwhile, the release of Granzyme B, IFN-γ, IL-2, and TNF-α in the 19-CD28M-CAR T cells decreased by 14%, 28%, 34%, and 33%, respectively. The results indicate that while the cytotoxicity of CD19-CAR T cells with mutations in the CD28 costimulatory domain does not cause weakened killing activity, the safety is significantly enhanced.
  

  
  
• Select
  Regulation of polysaccharide of Fructus Corni on the immune function of immunosuppressive mice

  SHI He-yuan, SANG Hong-ling, TAN Ai-hua, TAN Zheng-wei, ZHAO Min

  2022, 42(6): 482-488.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The goal of this study was to understand the effect and mechanism of polysaccharide of Fructus Corni (PFC) on the immune response of cyclophosphamide (CTX) induced immunosuppressive mice. Mice were randomly divided into the normal group (control group), immunosuppressive model group (CTX group), low-dose PFC group (CTX+LD group), medium-dose PFC group (CTX+MD group), and high-dose PFC group (CTX+HD group), with 12 mice per group. The immunosuppressive mouse model was established using intraperitoneal injection of CTX. The treatment groups were given a corresponding dose of PFC solution by gavaging. At the end of the treatments, the peritoneal macrophages' phagocytic capacity was detected by carbon particle clearance test, the spleen pathological change by H-E staining, and the amount of Lactobacillus, Bifidobacterium and Escherichia coli in the intestine by colony counting. In addition, the percentage of CD4+ and CD8+T cells in the spleen was detected by FACS, the expression levels of serum IL-2 and IL-10 were measured by ELISA and the protein levels of IFN-γ, IL-2, IL-4, IL-10, T-box transcription factor (T-bet) and GATA binding protein 3 (GATA3) in the spleen tissue were detected by Western blotting. The results showed that, compared to the control group, the clearance index, phagocytic index, splenic CD4+, CD8+T cell percentages and CD4+/CD8+T cell ratio in the CTX group were all significantly decreased (all with P＜0.05). The amount of intestinal Lactobacillus and Bifidobacterium was also significantly decreased (both with P＜0.05), while the number of Escherichia coli was significantly increased (P＜0.05). At the same time, the serum level of IL-2 was significantly decreased (P＜0.05), whereas the expression of IL-10 was significantly increased (P＜0.05). The spleen of the CTX group showed tissue damage and the expressions of T-bet, IFN-γ and IL-2 protein in the spleen significantly decreased (all with P＜0.05), while those of GATA3, IL-10, and IL-4 protein significantly increased (all with P＜0.05). Compared to the CTX group, the clearance index, phagocytic index, CD4+, CD8+T cell frequencies, and CD4+/CD8+T cell ratio in the spleen of mice treated with medium- or high-dose PFC were significantly increased (all with P＜0.05). The amount of intestinal Lactobacillus and Bifidobacterium was also significantly increased (both with P＜0.05), while the number of Escherichia coli was significantly decreased (P＜0.05). The expression of IL-2 in the serum of PFC-treated mice was significantly increased whereas the expression of IL-10 was significantly decreased (both with P＜0.05). In addition, the PFC groups showed alleviated spleen tissue damage, and the protein levels of T-bet, IFN-γ and IL-2 were significantly increased (all with P＜0.05), while those of GATA3, IL-10, and IL-4 were significantly decreased (all with P＜0.05). In summary, our results suggest that PFC may improve the immune function of CTX-induced immunosuppressive mice. The underlying mechanism may involve the regulation of intestinal flora composition and Th1/Th2 ratio.
• Select
  miR-433-3p inhibits IL-17 mediated proliferation, migration, and invasion of lung cancer cells by targeting SMC4

  JING Hong-jia, LIU Jian-wei, MA Jian-xin, LI Xiao-feng, QI Ying-song

  2022, 42(6): 489-498.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The goal of this study is to investigate the mechanism of IL-17 on the proliferation, migration, and invasion of lung cancer cells. A549 and HCC827 lung cancer cells were treated with IL-17 (20 ng/mL) for 48 h and Western blotting, qRT-PCR, Transwell analysis, MTT analysis, and dual luciferase reporter gene experiments were performed respectively to detect the protein levels of Cyclin D1, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), cyclin-dependent kinase inhibitor protein (p21) and structural maintenance of chromosome 4 (SMC4); the mRNA expression of miR-433-3p and SMC4; cell proliferation, migration, invasion, and luciferase activity of the two cancer cells lines. The results showed that compared with the control group, the proliferation, migration, and invasion of A549 and HCC827 cells in the IL-17-treated groups were significantly increased (P<0.05), while the expression level of miR-433-3p was significantly decreased (P<0.05). Meanwhile, the expressions of SMC4, Cyclin D1, MMP-2， and MMP-9 were all up-regulated (P<0.05). miR-433-3p had a binding site with SMC4. Compared with the anti-miR-NC group and the pcDNA group, the proliferation, migration, and invasion abilities of A549 and HCC827 cells in the anti-miR-433-3p group and the pcDNA-SMC4 group were significantly increased (P<0.05). At the same time, the levels of Cyclin D1, MMP-2, and MMP-9 were significantly up-regulated (P<0.05). Therefore, miR-433-3p may inhibit IL-17-induced cell proliferation, migration, and invasion, and downregulate the levels of Cyclin D1, MMP-2, and MMP-9. Together, this study suggests that IL-17 contributes to the proliferation, migration, and invasion of lung cancer cells, possibly by inhibiting the activity of the miR-433-3p/SMC4 pathway.
• Select
  circ_0060745 targets miR-194 and regulates LPS-induced inflammatory injury on bronchial epithelial cells

  SONG Bin, GE Hong, LI Ning

  2022, 42(6): 499-504.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  To  investigate the effect of miR-194 targeted circ_ular RNA 0060745 (circ_0060745) on LPS-induced inflammatory injury of bronchial epithelial cell 16HBE, 16HBE cells were stimulated with 50 μg/mL LPS for 24 hours and RT-qPCR was used to analyze the expression of circ_0060745 and miR-194. FACS was applied to detect cell apoptosis rate and ELISA was used to measure the levels of IL-6 and TNF-α in cell supernatant. circ_0060745 small interfering RNA(siRNA) and miR-194 mimics were transfected into 16HBE cells, respectively, to manipulate the expression levels of circ_0060745 or miR-194. Dual luciferase reporter gene assay and RT-qPCR were used to analyze the interaction between circ_0060745 and miR-194. The results showed that the apoptosis rate, the levels of IL-6 and TNF-α and the expression of circ_0060745 in 16HBE cells treated with LPS were all significantly increased (all with P＜0.05), while the expression of miR-194 was significantly decreased (P＜0.05). Down-regulation of circ_0060745 or over-expression of miR-194 alleviated LPS-induced apoptosis and inflammatory damage of 16HBE cells (all with P＜0.05). circ_0060745 directly bounded to miR-194 and negatively regulated the expression of miR-194 (P＜0.05). In contrast, down-regulating miR-194 reversed the effect of circ_0060745 inhibition on LPS-induced apoptosis and inflammation of 16HBE cells (all with P＜0.05). In conclusion, down-regulating circ_0060745 alleviates LPS-induced apoptosis and inflammation of bronchial epithelial cells possibly by direct up-regulation of miR-194 expression.
• Select
  Alteration of serum Th1/Th2 cytokines in perimenopausal depression patients correlates with clinical outcome

  LIU Xiao-li, WANG Ke-fang

  2022, 42(6): 505-510.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  This study aims to investigate the changes and significance of serum Th1/Th2 cytokines in perimenopausal depression patients. The serum levels of Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α), neurotransmitters (5-hydroxytryptamine ［5-HT］, and norepinephrine ［NE］) were measured in both the perimenopausal depression patients group (disease group) and healthy perimenopausal women group (control group) and the correlation between Th1/Th2 cytokines and neurotransmitters, severity of illness (Hamilton depression scale-17, HAMD-17), and patient prognosis were analyzed. The results showed that the serum levels of IL-2, IL-6, IFN-γ and TNF-α in the disease group were higher than those in the control group (P<0.05), whereas the serum levels of IL-4, IL-10, 5-HT, and NE in the disease group were lower than those in the control group (P<0.05). In addition, the serum levels of IL-2, IL-6, IFN-γ, and TNF-α were negatively correlated with those of 5-HT and NE (P<0.05), while positively correlated with the HAMD-17 scale score (P<0.05). In contrast, the serum levels of IL-4 and IL-10 were positively correlated with those of 5-HT and NE (P<0.05), but negatively correlated with the HAMD-17 scale score (P<0.05). The levels of serum IL-2, IL-6, IFN-γ, and TNF-α in patients with mild, moderate, and severe symptoms showed progressive increase following the severity of the disease (P<0.05), while the levels of serum IL-4 and IL-10 were  decreased accordingly (P<0.05). The serum levels of IL-2, IL-6, IFN-γ, and TNF-α were negatively correlated with the patient outcome: lowest in recovered patients and increased duly in markedly effective, progressive, and ineffective patients (P<0.05), whereas the serum levels of IL-4 and IL-10 followed the opposite trend (P<0.05). The study suggests that the levels of IL-2, IL-6, IFN-γ, and TNF-α in Th1/Th2 cytokines are increased in perimenopausal depression patients, while the levels of IL-4 and IL-10 are decreased. In addition, these changes correlate with the severity and prognosis of the disease, as well as with the serum levels of neurotransmitters.
  

  
  
• Select
  The correlation of IgA nephropathy and dysfunctional intestinal flora

  FAN Xiao-min, MI Yan, WANG Cai-li

  2022, 42(6): 511-515.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  IgA nephropathy (IgAN) is the most common type of primary glomerular disease with some patients eventually progressing to end-stage renal disease. The pathogenesis of IgAN is yet to be elucidated and one of the hypotheses is the “gut-kidney axis” in which IgAN is believed to be closely related to mucosal immune response and intestinal flora disorder. This review summarizes the characteristics of intestinal flora in IgAN patients to understand the pathogenesis of IBD. It also discusses the treatment options of IgAN and provides new directions for the clinical treatment of IgAN by targeting intestinal flora. 
• Select
  The regulatory role of JAK/STAT/SOCS signaling pathway on Th17/Treg balance in liver disease

  ZHANG Ru-yi, LIU Huai-e, YOU Jing, PENG Yu-juan

  2022, 42(6): 516-521.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Th17 and Treg are two subsets of CD4⁺T lymphocytes. These two types of cells maintain optimal balance in a normal physiological state, whereas the Th17/Treg balance is disturbed in the disease state. Multiple signaling pathways are involved in the maintenance of Th17/Treg balance, among which JAK/STAT/suppressors of cytokine signaling（SOCS）, especially JAK/STAT/SOCS1 and SOCS3 are essential for maintaining the Th17/Treg balance. Studies have shown that Th17/Treg imbalance happens in viral hepatitis, autoimmune liver disease, and nonalcoholic fatty liver disease, and the imbalance correlates with the severity of the disease. SOCS1 and SOCS3 regulate the Th17/Treg balance through the JAK/STAT signaling pathway. This review focuses specifically on the regulatory role of the JAK/STAT/SOCS signaling pathway on Th17/Treg balance in liver diseases. 
  

  
  
• Select
  Research progress of dendritic cells in the pathogenesis of osteoarthritis

  ZHANG Hui, DUAN Li, WANG Da-ping, ALAHDAL Murad

  2022, 42(6): 522-526.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  As the most common chronic progressive joint disease, osteoarthritis (OA) is characterized by the destruction of articular cartilage. As a powerful type of APC, DC are closely related to the damage and repair of articular cartilage. Although few DCs are located in the articular fluid and bone marrow, their existence is positively correlated with OA severity. Matrix metalloproteinase (MMP), the main collagenase in OA cartilage, is closely related to the number of a subtype of DC: plasmacytoid dendritic cell (pDC). DC promotes the differentiation of type B synovial cells and plays an important role in the early stage of OA. In joint fluid, DC releases a variety of inflammatory factors to promote OA-related synovial inflammation. This review discusses the role of DCs in OA pathogenesis.
  

  
  
• Select
  The role of the complement system in the pathogenesis of inflammatory bowel disease

  CAO Hui, LIU Su-xian, WEN Hong-zhu, LIN Jiang

  2022, 42(6): 527-531.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Inflammatory bowel disease (IBD) is an autoimmune disease characterized by intestinal chronic inflammation. The onset of intestinal chronic inflammation in IBD is associated with the impaired integrity of the physiological barrier, the dysfunction of the chemical barrier, and the disorder of homeostasis of the immunological barrier of the intestine. As an important component of innate immunity, the complement system sustains the gut function by maintaining the integrity of the physiological barrier, the function of the chemical barrier, and the homeostasis of the immunological barrier of the intestine. The abnormal activation of the complement system may be one of the crucial factors causing intestinal inflammation in IBD. This review discusses the potential role of the complement system in the pathogenesis of IBD and summarized the differences between the physiological and IBD states of the intestinal barrier. 
• Select
  Research progress on the relationship between pyroptosis and kidney diseases

  MA Xiang-ying, ZHANG Zhi-heng, SHEN Mei-lun, LI Rou-qian, JIN Xiao-di, GAO Li

  2022, 42(6): 532-535.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Pyroptosis is a new type of programmed cell death with some characteristics similar to apoptosis and necrosis. In order to explore the mechanisms of pyroptosis in kidney diseases, this review compares the expression of pyroptosis-related proteins in disease models including acute kidney injury, chronic kidney disease and diabetic nephropathy. In pathologic kidney tissues, the expressions of NLRP3 and caspase proteins are up-regulated and in turn gasdermin D (GSDMD) is cleaved which ruptures the cell membrane and releases inflammatory cytokines IL-1β and IL-18 to induce pyroptosis. Therefore, in many kidney diseases, NLRP3-caspase-GSDMD-IL-1β/IL-18 axis mediates the inflammatory response and promotes the disease development. This review aims to elucidate the relationship between pyroptosis and kidney diseases.
  

  
  
• Select
  Research advances on the role and mechanism of neutrophil extracellular trap in autoimmune diseases

  ZHANG Li-jie, DANG Wan-tai

  2022, 42(6): 536-540.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Neutrophil is considered as a type of innate immune phagocyte and plays a central role in immune defense. Recent studies showed that neutrophil extracellular trap (NET) is a key element in the pathogenesis of autoimmune diseases. In addition to attracting and killing pathogens, NET may also cause direct or indirect organ damage. The correlation between NETs and autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, has already been proven. With the formation of NET, a large amount of autoantigens are exposed and when the autoantigens cannot be removed in a timely fashion, they will lead to the production of autoantibodies, which in turn cause the aggravation of autoimmune diseases. This review summarizes the function and mechanism of NETs in autoimmune diseases and thus provides constructive insights for understanding the pathogenesis and developing targeted therapy for related diseases.
• Select
  Research progress of circular RNAs in systematic lupus erythematosus

  LIN Xiao-bing, LIANG Xiao-feng, PENG Zhi-shen, LIN Zi-en, LIN Wei-yi, WEI Shan-shan

  2022, 42(6): 541-546.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  circular RNA (circ_RNA) is a special type of endogenous regulatory RNA with a closed circular structure. It functions as a "molecular sponge" of miRNA as well as a regulator of gene transcription and expression, making it a critical component in the occurrence and development of many diseases. In recent years, multiple studies confirm that circ_RNAs are differentially expressed in systemic lupus erythematosus （SLE） patients and normal healthy people, and some circ_RNAs are involved in the pathological process of SLE. Therefore, circ_RNAs are potential biomarkers for early diagnosis and prognosis assessment of SLE, as well as therapeutic targets. This review summarizes the research progress of circ_RNA in SLE and aims to provide new directions for the diagnosis, prognosis, and treatment of SLE.
• Select
  Research progress on the osteoimmunomodulation by metal ions

  CHEN Ding, LI Fu-yao, JIANG Qian-zhou, GUO Lü-hua

  2022, 42(6): 547-550.

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Metal ions regulate cellular responses in vivo by participating in the transduction of signals inside and outside the cell. In the local bone microenvironment, metal ions are important immunomodulators. They not only induce macrophages to polarize to different phenotypes but also regulate the secretion of various cytokines. Macrophage-mediated osteoimmunomodulation revolves around the regulation of immune cells to maintain an optimal immune microenvironment and accelerate the repair and regeneration of bone tissue. This review discusses the regulation of metal ions on osteoimmunomodulation.