Grigg John B, Shanmugavadivu Arthi, Regen Tommy, Parkhurst Christopher N, Ahmed Anees, Joseph Ann M, Mazzucco Michael, Gronke Konrad, Diefenbach Andreas, Eberl Gerard, Vartanian Timothy, Waisman Ari, Sonnenberg Gregory F
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Nature. 2021 Dec;600(7890):707-712. doi: 10.1038/s41586-021-04136-4. Epub 2021 Dec 1.
Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases, but the pathways that control these responses remain unclear. Here we define a population of inflammatory group 3 innate lymphoid cells (ILC3s) that infiltrate the CNS in a mouse model of multiple sclerosis. These ILC3s are derived from the circulation, localize in proximity to infiltrating T cells in the CNS, function as antigen-presenting cells that restimulate myelin-specific T cells, and are increased in individuals with multiple sclerosis. Notably, antigen presentation by inflammatory ILC3s is required to promote T cell responses in the CNS and the development of multiple-sclerosis-like disease in mouse models. By contrast, conventional and tissue-resident ILC3s in the periphery do not appear to contribute to disease induction, but instead limit autoimmune T cell responses and prevent multiple-sclerosis-like disease when experimentally targeted to present myelin antigen. Collectively, our data define a population of inflammatory ILC3s that is essential for directly promoting T-cell-dependent neuroinflammation in the CNS and reveal the potential of harnessing peripheral tissue-resident ILC3s for the prevention of autoimmune disease.
中枢神经系统（CNS）中的促炎性T细胞与多种脱髓鞘和神经退行性疾病存在因果关联，但控制这些反应的途径仍不清楚。在这里，我们定义了一群炎症性3型固有淋巴细胞（ILC3s），它们在多发性硬化症小鼠模型中浸润中枢神经系统。这些ILC3s来源于循环系统，定位于中枢神经系统中浸润性T细胞附近，作为抗原呈递细胞重新刺激髓鞘特异性T细胞，并且在多发性硬化症患者中数量增加。值得注意的是，炎症性ILC3s的抗原呈递对于促进中枢神经系统中的T细胞反应以及小鼠模型中多发性硬化症样疾病的发展是必需的。相比之下，外周的传统和组织驻留ILC3s似乎对疾病诱导没有贡献，而是在实验性地靶向呈递髓鞘抗原时限制自身免疫性T细胞反应并预防多发性硬化症样疾病。总体而言，我们的数据定义了一群炎症性ILC3s，它们对于直接促进中枢神经系统中T细胞依赖性神经炎症至关重要，并揭示了利用外周组织驻留ILC3s预防自身免疫性疾病的潜力。
