Gao Yaxian, Xia Dongshuai, You Yong, Cheng Yu, Bai Bing, Feng Guiying, Liang Xiujun, Cheng Luyang, Song Hongru, Wang Yongwei
Department of Immunology, Basic Medical Institute, Chengde Medical University, Chengde 067000 Hebei, China.
Central Laboratory, Clinical Laboratory Center, Affiliated Taian City Central Hospital of Qingdao University, Taian 271000 Shandong, China.
Int Immunopharmacol. 2025 Feb 6;147:114028. doi: 10.1016/j.intimp.2025.114028. Epub 2025 Jan 10.
Rheumatoid arthritis (RA) is a systemic autoimmune disease, and TL1A and its receptor DR3 play important roles in its pathogenesis. Th9 cells are involved in RA development. Dioscin from Dioscorea nipponica (DDN) has a therapeutic effect on RA, but its effect on TL1A/DR3 and Th9 cells remains unclear. A collagen-induced arthritis (CIA) model was established in DBA/1 mice, and the therapeutic effects of DDN were determined using pathological sections and arthritis index scores. Western blotting and PCR were used to detect TL1A, DR3, PU.1, TGF-β and IRF-4. Enzyme-linked immunosorbent assay was used to detect the expression of TL1A and IL-9 in the serum. Immunofluorescence was used to detect the localization and expression of TL1A, DR3, and PU.1 in synovial tissue. Flow cytometry was used to detect TL1A and DR3 expression in different immune cells and Th9 cells. DDN ameliorated bone destruction, inflammatory cell infiltration, synovial inflammation, cartilage tissue destruction, and proteoglycan loss. DDN downregulated TL1A, DR3, and PU.1 in the synovium of the lymph nodes and spleen and TL1A and IL-9 in the serum. DDN decreased the number of TL1A-expressing APCs and macrophages, DR3-expressing CD4 + T cells, and Th9 cells. Th9 cell differentiation-related factors TGF-β and IRF-4 were also inhibited by DDN. We conclude that DNN inhibited the expression of TL1A/DR3 in CIA mice and suppressed the expression of the Th9 cell-specific transcription factor PU.1, Th9 cell number, and IL-9 secretion. DDN inhibited the function of Th9 cells by targeting TGF-β and IRF-4 in the TL1A/DR3 pathway, thereby reducing inflammation.
类风湿关节炎（RA）是一种全身性自身免疫性疾病，而肿瘤坏死因子样凋亡微弱诱导因子（TL1A）及其受体死亡受体3（DR3）在其发病机制中起重要作用。辅助性T细胞9（Th9细胞）参与类风湿关节炎的发展。穿龙薯蓣中的薯蓣皂苷（DDN）对类风湿关节炎有治疗作用，但其对TL1A/DR3和Th9细胞的影响尚不清楚。在DBA/1小鼠中建立胶原诱导性关节炎（CIA）模型，并通过病理切片和关节炎指数评分确定DDN的治疗效果。采用蛋白质免疫印迹法和聚合酶链反应检测TL1A、DR3、PU.1、转化生长因子-β（TGF-β）和干扰素调节因子4（IRF-4）。采用酶联免疫吸附测定法检测血清中TL1A和白细胞介素-9（IL-9）的表达。采用免疫荧光法检测滑膜组织中TL1A、DR3和PU.1的定位和表达。采用流式细胞术检测不同免疫细胞和Th9细胞中TL1A和DR3的表达。DDN改善了骨破坏炎症细胞浸润、滑膜炎、软骨组织破坏和蛋白聚糖丢失。DDN下调了淋巴结和脾脏滑膜中TL1A、DR3和PU.1以及血清中TL1A和IL-9的表达。DDN减少了表达TL1A的抗原呈递细胞（APC）和巨噬细胞数量以及表达DR3的CD4 + T细胞和Th9细胞数量。Th9细胞分化相关因子TGF-β和IRF-4也受到DDN的抑制。我们得出结论，DDN抑制了CIA小鼠中TL1A/DR3的表达，抑制了Th9细胞特异性转录因子PU.1的表达、Th9细胞数量以及IL-9分泌。DDN通过靶向TL1A/DR3途径中的TGF-β和IRF-4抑制Th9细胞功能，从而减轻炎症。
