TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2019 Sep 19

PMID 31533032

Citations 128

Authors

Tianqi Leng

Hossain Delowar Akther

Carl-Philipp Hackstein

Kate Powell

Thomas King

Matthias Friedrich

Zoe Christoforidou

Sarah McCuaig

Mastura Neyazi

Carolina V Arancibia-Carcamo

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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MAIT cell homing in intestinal homeostasis and inflammation.

Wu Z, Chen X, Han F, Leeansyah E Sci Adv. 2025; 11(6):eadu4172.

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Human MAIT cell response profiles biased toward IL-17 or IL-10 are distinct effector states directed by the cytokine milieu.

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Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.

Walkenhorst M, Sonner J, Meurs N, Engler J, Bauer S, Winschel I Nat Commun. 2024; 15(1):9287.

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MAIT cells: Conserved watchers on the wall.

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