TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions
Leng T., Akther HD., Hackstein C-P., King T., Friedrich M., Christoforidou Z., McCuaig S., Neyazi M., Arancibia-Cárcamo CV., Powrie F., Marchi E., Peres RS., Millar V., Ebner D., Willberg C., Klenerman P.
<jats:title>SUMMARY</jats:title><jats:p>MAIT cells are an abundant T-cell population enriched in peripheral tissues such as the liver. They are activated both through TCR-dependent and - independent mechanisms. However, the different specific functional responses of MAIT cells to these distinct signals remain elusive. We examined the impact of combinations of TCR-dependent and -independent signals in blood and tissue-derived human MAIT cells. TCR-independent activation of MAIT cells from blood and gut was maximised by extending the panel of cytokines to including TNF-superfamily member TL1A. RNAseq experiments revealed that TCR-dependent and -independent signals drive MAIT cells to exert overlapping and unique effector functions, impacting both host defence and tissue homeostasis. While TCR-triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells did show specific enrichment of tissue-repair functions at the level of gene expression, protein production and in <jats:italic>in vitro</jats:italic> assays and these functions were amplified by cytokine costimulation. Taken together, these data indicate the blend of TCR-dependent and -independent signalling to MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.</jats:p>