Huachen Huang, Gaoyu Liu, Yali Han, Yuyang Miao, Zhibao Zhu, Ying Wang, Jianye Wang, Mengxuan Shi, Jinyi Li, Huaijin Yang, Tongxiao Xu, Caiyun Qi, Jinhao Yang, Wenjun Zhang, Zhaoli Han, Bingbing Wang, De-Cai Tian, Ying Fu, Jie Zhou, Qiang Liu
The meninges are a gateway for pathogenic T cells to enter the central nervous system (CNS). They possess a diverse repertoire of immune cells that orchestrate CNS inflammation and autoimmunity, yet the underlying mechanisms are poorly understood. Here, we report that group 2 innate lymphoid cells (ILC2s) accumulated in the dura as experimental autoimmune encephalomyelitis (EAE) progressed. Single-cell RNA sequencing and flow cytometry analyses revealed distinct features of ILC2s, including expression of MHC class II. ILC2s acted as antigen-presenting cells to activate and expand myelin-reactive T cells in an MHC class II-dependent manner. ILC2-mediated expansion of myelin-reactive T cells increased expression of cytokines IFN-γ and IL-17A. Genetic ablation of ILC2s or of H2-Ab1 in ILC2s alleviated neuroinflammation and CNS demyelination during EAE. These findings revealed a role of ILC2s in neuroinflammation via instructing myelin-reactive T cells, implying targeting ILC2s may be an avenue to restrict CNS inflammation and autoimmunity.