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T-bet-dependent NKp46(+) innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.

Kwong, B;Rua, R;Gao, Y;Flickinger, J;Wang, Y;Kruhlak, MJ;Zhu, J;Vivier, E;McGavern, DB;Lazarevic, V;

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(+) TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46(+) ILCs profoundly impaired the ability of myelin-reactive TH17 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.