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Antigen-presenting innate lymphoid cells orchestrate neuroinflammation
Nature ( IF 64.8 ) Pub Date : 2021-12-01 , DOI: 10.1038/s41586-021-04136-4
John B Grigg 1, 2, 3 , Arthi Shanmugavadivu 4 , Tommy Regen 4 , Christopher N Parkhurst 1, 2, 3 , Anees Ahmed 1, 2, 3 , Ann M Joseph 1, 2, 3 , Michael Mazzucco 5 , Konrad Gronke 6, 7 , Andreas Diefenbach 6, 7 , Gerard Eberl 8 , Timothy Vartanian 5 , Ari Waisman 4 , Gregory F Sonnenberg 1, 2, 3
Affiliation  

Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases1,2,3,4,5,6, 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.



中文翻译:

抗原呈递先天性淋巴样细胞协调神经炎症

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有因果关系1,2,3,4,5,6, 但控制这些反应的途径仍不清楚。在这里,我们定义了在多发性硬化症小鼠模型中浸润 CNS 的炎症第 3 组先天性淋巴样细胞 (ILC3) 群体。这些 ILC3 来源于循环,定位于 CNS 中浸润性 T 细胞附近,作为抗原呈递细胞重新刺激髓磷脂特异性 T 细胞,并在多发性硬化症患者中增加。值得注意的是,炎症性 ILC3 的抗原呈递对于促进 CNS 中的 T 细胞反应和小鼠模型中多发性硬化样疾病的发展是必需的。相比之下,外周的常规和组织驻留的 ILC3 似乎对疾病诱导没有贡献,而是限制自身免疫性 T 细胞反应,并在实验性靶向呈递髓磷脂抗原时预防多发性硬化症样疾病。总的来说,我们的数据定义了炎症性 ILC3 群体,这对于直接促进中枢神经系统中的 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 ILC3 预防自身免疫性疾病的潜力。

更新日期:2021-12-01
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