This study investigated the role of IL-33 knockdown in attenuating airway inflammation in a mouse asthma model, aiming to identify novel therapeutic targets for asthma. Bone marrow-derived mesenchymal stem cells(BMMSC) were isolated from mice and transduced with IL-33-silencing plasmids(si-IL-33-1^#, si-IL-33-2^#, si-IL-33-3^# and a scrambled control plasmid) via lentiviral system. The efficiency of IL-33 knockdown was validated by qRT-PCR. An asthma mouse model was established using a combined sensitization and challenge protocol with ovalbumin(OVA). Mice were divided into 5 groups: the control group; the asthma model group; the BMMSC-treated group; the BMMSC+empty vector group and the BMMSC+IL-33 knockdown group. Pathological changes in lung tissues were assessed by H-E staining, Masson's trichrome staining, and immunohistochemistry(IHC). Serum levels of IL-33, IL-1β, and IL-6 were quantified using ELISA. The result showed that primary BMMSC exhibited adherent growth with spindle or polygonal morphology. Flow cytometry was used to measure the expressions of surface markers: CD90 positivity rate was 99.30%; CD29 positivity rate was 100.00%; while hematopoietic lineage markers CD45 and CD34 showed minimal positivity(0.34% and 1.24%, respectively). qRT-PCR demonstrated that the si-IL-33-3^# plasmid effectively silenced IL-33 expression in BMMSC, confirming that it was an optimal IL-33 knockdown construct. Histopathological analysis revealed the BMMSC+IL-33 knockdown group displayed minimal inflammatory cell infiltration in lung tissue, with intact bronchial epithelium. IHC staining showed that BMMSC+IL-33 knockdown group exhibited significantly reduced α-smooth muscle actin(α-SMA) and vascular endothelial growth factor B(VEGFB) relative expressions compared to those in the asthma model group and the BMMSC-treated group(P<0.05). ELISA analysis further confirmed the markedly decreased serum levels of IL-1β, IL-6, and IL-33 in the BMMSC+IL-33 knockdown group compared to either the model or the BMMSC-treated groups(P<0.05). Altogether, IL-33 knockdown attenuates inflammatory response in the asthma mouse model and thereby prevents the lung lesions associated with asthma.

为了研究4型肽基精氨酸脱亚胺酶(peptidyl arginine deimidase type 4, PAD4)在炎症脂肪组织中的作用及机制,分别提取db/db[Ⅱ型糖尿病(type 2 diabetes mellitus, T2DM)组]、db/m(T2DM对照组)、ob/ob(肥胖组)和ob/c(肥胖对照组)4组小鼠皮下和内脏脂肪组织，免疫组化技术检测PAD4在T2DM和肥胖小鼠皮下和内脏脂肪组织中的表达情况；LPS刺激野生型小鼠原代腹腔巨噬细胞和小鼠巨噬细胞系RAW264.7，qRT-PCR和Western blotting检测两种细胞中PAD4、炎性因子TNF-α和IL-6的表达以及NF-κB信号通路的激活情况。结果显示，与db/m、ob/c两组小鼠相比，db/db、ob/ob两组小鼠中皮下和内脏脂肪组织、经LPS刺激的小鼠原代腹腔巨噬细胞和RAW264.7细胞中PAD4的表达均降低，炎性因子TNF-α和IL-6的表达均明显升高；同时TLR4/NF-κB信号通路激活。该研究表明PAD4在炎症状态下(T2DM和肥胖)的皮下和内脏脂肪组织中表达下降，并与TLR4/NF-κB信号通路激活呈负相关。

Peripheral helper T cells (Tph) have been identified in recent years as a CD4⁺ T cell subset. Tph are characterized by the secretion of  C-X-C motif chemokine ligand 13 (CXCL13), and the expression of surface molecules including PD-1, inducible costimulatory  (ICOS), HLA-DR, etc. By expressing chemokine receptor C-C motif chemokine receptor 2 (CCR2), C-X3-C motif chemokine receptor 1 (CX3CR1), and CCR5, Tph can be recruited to inflammatory sites and promote the formation of tertiary lymphoid structures (TLS). Through interaction with IL-21 and signaling lymphocytic activation molecule family (SLAMF), Tph assist B cell maturation, differentiation, and antibody production. Tph are shown to be involved in the pathogenesis of many autoimmune diseases. Herein, this review discusses the biological characteristics of Tph and their role in different types of autoimmune diseases to further reveal their mechanism of action and clinical value, and provide new ideas for future targeted therapy.