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Recipient mucosal-associated invariant T cells control GVHD within the colon

Varelias, Antiopi, Bunting, Mark D., Ormerod, Kate L., Koyama, Motoko, Olver, Stuart D., Straube, Jasmin, Kuns, Rachel D., Robb, Renee J., Henden, Andrea S., Cooper, Leanne, Lachner, Nancy, Gartlan, Kate H., Lantz, Olivier, Kjer-Nielsen, Lars, Mak, Jeffrey Y.W., Fairlie, David P., Clouston, Andrew D., McCluskey, James, Rossjohn, Jamie, Lane, Steven W., Hugenholtz, Philip and Hill., Geoffrey R. 2018. Recipient mucosal-associated invariant T cells control GVHD within the colon. Journal of Clinical Investigation 128 (5) , pp. 1919-1936. 10.1172/JCI91646

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Abstract

Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I–like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT. Allogeneic BMT recipients deficient in IL-17A also develop accelerated GVHD, suggesting MAIT cells likely regulate GVHD, at least in part, by the generation of this cytokine. Indeed, analysis of stool microbiota and colon tissue from IL-17A–/– and MR1–/– mice identified analogous shifts in microbiome operational taxonomic units (OTU) and mediators of barrier integrity that appear to represent pathways controlled by similar, IL-17A–dependent mechanisms. Thus, MAIT cells act to control barrier function to attenuate pathogenic T cell responses in the colon and, given their very high frequency in humans, likely represent an important population in clinical BMT.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 19 April 2018
Date of Acceptance: 16 February 2018
Last Modified: 15 Aug 2018 14:12
URI: http://orca.cf.ac.uk/id/eprint/110799

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