An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease.
An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease.
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DOI：
10.1084/jem.187.4.537
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发表时间：
1998-02-16
期刊：
影响因子：
--
通讯作者：
Shevach EM
中科院分区：
文献类型：
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作者：
Segal BM;Dwyer BK;Shevach EM
先天免疫系统的细胞在免疫反应早期分泌细胞因子，引导成熟的 T 辅助细胞 (Th) 沿着适当的谱系生长。本研究探讨了细胞因子网络在器官特异性自身免疫性疾病发病机制中的作用，它连接了先天性和后天性免疫系统。实验性过敏性脑脊髓炎（EAE）是一种中枢神经系统脱髓鞘疾病，被广泛用作多发性硬化症的动物模型。我们证明，无论存在或不存在干扰素 γ，白细胞介素 (IL)-12 对于诱导 EAE 的自身反应性 Th1 细胞的生成至关重要。 IL-12 的疾病促进作用被抗原非特异性 CD4+ T 细胞产生的 IL-10 拮抗，而 IL-10 又受到 IL-12 内源性产生的调节。这种独特的免疫调节回路似乎在控制 Th 细胞分化中发挥着关键作用，并提供了一种机制，通过该机制，先天免疫系统的微生物触发因素可以调节自身免疫性疾病。
Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon γ. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.