[PDF][PDF] TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions

T Leng, HD Akther, CP Hackstein, K Powell, T King… - Cell reports, 2019 - cell.com
T Leng, HD Akther, CP Hackstein, K Powell, T King, M Friedrich, Z Christoforidou…
Cell reports, 2019cell.com
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 …
Summary
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 tissue-repair 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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