T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.
Brandon KwongRejane RuaYuanyuan GaoJohn FlickingerYan WangMichael J KruhlakJinfang ZhuÉric VivierDorian B McGavernVanja LazarevicPublished in: Nature immunology (2017)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- nk cells
- transcription factor
- traumatic brain injury
- poor prognosis
- oxidative stress
- blood brain barrier
- lipopolysaccharide induced
- endoplasmic reticulum stress
- signaling pathway
- metabolic syndrome
- type diabetes
- cognitive impairment
- skeletal muscle
- drug induced
- pi k akt
- cell proliferation
- white matter
- endothelial cells
- cerebrospinal fluid
- subarachnoid hemorrhage
- dna binding