The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46⁺ innate lymphoid cells (ILCs) in the initiation of CD4⁺ T_H17-mediated neuroinflammation. Loss of T-bet specifically in NKp46⁺ ILCs profoundly impaired the ability of myelin-reactive T_H17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity. T-bet-dependent NKp46⁺ ILCs localized in the meninges and acted as chief coordinators of meningeal inflammation by inducing the expression of proinflammatory cytokines, chemokines and matrix metalloproteinases, which together facilitated T cell entry into CNS parenchyma. Our findings uncover a detrimental role of T-bet-dependent NKp46⁺ ILCs in the development of CNS autoimmune disease.

中文翻译：

---

T-bet依赖性NKp46 +先天性淋巴样细胞调节TH17诱导的神经炎症的发作

转录因子T-bet与系统性和器官特异性自身免疫的易感性增加有关，但T-bet表达促进神经炎症的机制尚不清楚。在这项研究中，我们证明T-bet依赖性NKp46 ⁺先天性淋巴样细胞（ILCs）在CD4 ⁺ T _H 17介导的神经炎症的起始中起着重要作用。在NKp46 ⁺ ILC中特异的T-bet缺失严重损害了髓磷脂反应性T _H 17细胞侵袭中枢神经系统（CNS）组织的能力，并保护了小鼠免于自身免疫。依赖T-bet的NKp46 ⁺ILC位于脑膜中，并通过诱导促炎细胞因子，趋化因子和基质金属蛋白酶的表达来充当脑膜炎症的主要协调者，共同促进T细胞进入中枢神经系统实质。我们的发现揭示了T-bet依赖性NKp46 ⁺ ILC在中枢神经系统自身免疫性疾病发展中的有害作用。