CD69 downregulates autoimmune reactivity through active transforn ing growth factor-β production in collagen-induced arthritis
CD69 downregulates autoimmune reactivity through active transforn ing growth factor-β production in collagen-induced arthritis
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DOI：
10.1172/jci200319112
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发表时间：
2003-09-01
影响因子：
15.9
通讯作者：
Sánchez-Madrid, F
中科院分区：
文献类型：
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作者：
Sancho, D;Gómez, M;Sánchez-Madrid, F
CD 69在炎症部位的白细胞活化后被诱导，但其在炎症过程中的生理作用仍然未知。我们通过分析WT和CD 69缺陷小鼠的胶原诱导性关节炎（CIA）模型，探讨了CD 69在自身免疫反应中的作用。CD 69（-/-）小鼠CIA发病率和严重程度较高，对II型胶原的T和B细胞免疫反应加剧。在CIA中作为保护剂的TGF-β 1和TGF-β 2的水平在CD 69-/-小鼠炎症灶中降低，与促炎细胞因子IL-1 β和RANTES的增加相关。局部注射阻断性抗TGF-β抗体增加了CD 69（+/+）小鼠CIA的严重程度和促炎细胞因子mRNA水平，但在CD 69-/-小鼠中没有。此外，在体外参与的CD 69诱导总的和积极的TGF-β 1的生产在刀豆球蛋白A激活的脾细胞亚群，小鼠和人类滑膜白细胞，和Jurkat稳定转染人CD 69，但不是在父母的CD 69阴性细胞系。我们的研究结果表明，CD 69是一种负调节剂的自身免疫反应性和炎症通过合成TGF-β，细胞因子，反过来下调各种促炎介质的产生。
CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69(-/-) mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-beta1 and TGF-beta2, which act as protective agents in CIA, were reduced in CD69-/- mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1beta and RANTES. Local injection of blocking anti-TGF-beta antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69(+/+) but not in CD69-/- mice. Moreover, in vitro engagement of CD69 induced total and active TGF-beta1 production in Concanavalin A-activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.