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

Publication date: 17 September 2019Source: Cell Reports, Volume 28, Issue 12Author(s): 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, Oxford IBD Investigators, Raphael Sanches Peres, Val Millar, Daniel Ebner, Rajesh Lamichhane, James Ussher, Timothy S.C. Hinks, Emanuele Marchi, Chris WillbergSummaryMAIT 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 inflamma...
Source: Cell Reports - Category: Cytology Source Type: research