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

Authors:

• Leng, Tianqi
• Akther, Hossain Delowar
• Hackstein, Carl-Philipp
• Powell, Kate
• King, Thomas
• Friedrich, Matthias
• Christoforidou, Zoe
• McCuaig, Sarah
• Neyazi, Mastura
• Arancibia-Cárcamo, Carolina V.
• Hagel, Joachim
• Powrie, Fiona
• Peres, Raphael Sanches
• Millar, Val
• Ebner, Daniel
• Lamichhane, Rajesh
• Ussher, James
• Hinks, Timothy S.C.
• Marchi, Emanuele
• Willberg, Chris
• Klenerman, Paul

Details:

Cell Reports, Volume 28, Issue 12, 2019-09-17

Article Link: Click here

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.