Journal
NATURE IMMUNOLOGY
Volume 18, Issue 10, Pages 1117-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3816
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Funding
- US National Institutes of Health, National Cancer Institute, Center for Cancer Research [ZIA BC 011431, ZIA BC 011432]
- National Institute of Neurological Disorders and Stroke [1ZIA NS 003111-08, 1ZIA NS 003112-08]
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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.
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