Nature Immunology
Nature Immunology
5 years ago

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

T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Dorian B McGavern, Michael J Kruhlak, Yuanyuan Gao, Yan Wang, Eric Vivier, Vanja Lazarevic, Jinfang Zhu, Brandon Kwong, John Flickinger, Rejane Rua
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.

Publisher URL: http://dx.doi.org/10.1038/ni.3816

DOI: 10.1038/ni.3816

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