Journal
CELL REPORTS
Volume 28, Issue 12, Pages 3077-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.08.050
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Funding
- Wellcome Trust [WT109965MA, 104553/z/14/z, 211050/Z/18/z]
- NIHR Senior Fellowship
- NIH [U19 I082360]
- Chinese Scholarship Council
- Deutsche Forschungsgemeinshaft (DFG) [403193363]
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
- Wellcome Trust [104553/Z/14/Z] Funding Source: Wellcome Trust
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MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8(+) MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissuerepair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8(+) MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.
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