Open AccessT-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Author(s) -
Brandon Kwong,
Réjane Rua,
Yuanyuan Gao,
John C. Flíckinger,
Yan Wang,
Michael J. Kruhlak,
Jinfang Zhu,
Éric Vivier,
Dorian B. McGavern,
Vanja Lazarevic
Publication year - 2017
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/ni.3816
Subject(s) - neuroinflammation , innate lymphoid cell , autoimmunity , experimental autoimmune encephalomyelitis , inflammation , immunology , proinflammatory cytokine , biology , chemokine , t cell , microbiology and biotechnology , innate immune system , immune system
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 H 17-mediated neuroinflammation. Loss of T-bet specifically in NKp46 + ILCs profoundly impaired the ability of myelin-reactive T H 17 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.