학술논문
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
Document Type
article
Author
Tianqi Leng; Hossain Delowar Akther; Carl-Philipp Hackstein; Kate Powell; Thomas King; Matthias Friedrich; Zoe Christoforidou; Sarah McCuaig; Mastura Neyazi; Carolina V. Arancibia-Cárcamo; Joachim Hagel; Fiona Powrie; Raphael Sanches Peres; Val Millar; Daniel Ebner; Rajesh Lamichhane; James Ussher; Timothy S.C. Hinks; Emanuele Marchi; Chris Willberg; Paul Klenerman
Source
Cell Reports, Vol 28, Iss 12, Pp 3077-3091.e5 (2019)
Subject
Language
English
ISSN
2211-1247
Abstract
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. : Leng et al. explore the consequences of activation of human MAIT cells via their TCR and/or cytokines, including the gut-associated TNF-superfamily member TL1A. TCR triggering reveals a transcriptional program linked to tissue-repair functions seen in vivo, consistent with a homeostatic role for these cells in epithelia. Keywords: MAIT cells, effector functions, TCR signaling, cytokines, tissue repair