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

Journal article

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.

Authors: Leng, T; Delowar Akther, H; Hackstein, C-P; Powell, K; King, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Cell Reports
• Volume: 28
• Issue: 12
• Pages: 3077-3091
• Publication date: 2019-09-17
• Acceptance date: 2019-08-16
• DOI: 10.1016/j.celrep.2019.08.050
• ISSN: 2211-1247
• Language: English
• Keywords: TCR signaling; tissue repair; FFR; cytokines; effector functions; MAIT cells