Department of Neuroimmunology, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
Nature. 2011 Oct 26;479(7374):538-41. doi: 10.1038/nature10554.
Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter. These pathogenic immune cells derive from progenitors that are normal, innocuous components of the healthy immune repertoire but become autoaggressive upon pathological activation. The stimuli triggering this autoimmune conversion have been commonly attributed to environmental factors, in particular microbial infection. However, using the relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis, here we show that the commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells. We show further that recruitment and activation of autoantibody-producing B cells from the endogenous immune repertoire depends on availability of the target autoantigen, myelin oligodendrocyte glycoprotein (MOG), and commensal microbiota. Our observations identify a sequence of events triggering organ-specific autoimmune disease and these processes may offer novel therapeutic targets.
活动多发性硬化病变显示出炎症变化，提示自身反应性 T 和 B 淋巴细胞联合攻击脑白质。这些致病免疫细胞来源于祖细胞，祖细胞是健康免疫库中的正常、无害成分，但在病理激活时变得自身攻击性。引发这种自身免疫转换的刺激物通常归因于环境因素，特别是微生物感染。然而，在这里，我们使用自发发展实验性自身免疫性脑脊髓炎的缓解-复发型小鼠模型表明，共生肠道菌群（在没有病原体的情况下）在引发免疫过程中是必不可少的，导致由髓鞘特异性 CD4(+) T 细胞驱动的缓解-复发自身免疫性疾病。我们进一步表明，自身抗体产生 B 细胞的募集和激活来自内源性免疫库，这取决于靶自身抗原髓鞘少突胶质细胞糖蛋白 (MOG)和共生微生物群的可用性。我们的观察结果确定了触发器官特异性自身免疫性疾病的一系列事件，这些过程可能为提供新的治疗靶点。
