β2 integrins differentially regulate γδ T cell subset thymic development and peripheral maintenance

McIntyre, C. L., Monin, L., Rop, J. C., Otto, T. D. , Goodyear, C. S. , Hayday, A. C. and Morrison, V. L. (2020) β2 integrins differentially regulate γδ T cell subset thymic development and peripheral maintenance. Proceedings of the National Academy of Sciences of the United States of America, 117(36), pp. 22367-22377. (doi: 10.1073/pnas.1921930117) (PMID:32848068)

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Abstract

The γδ T cells reside predominantly at barrier sites and play essential roles in immune protection against infection and cancer. Despite recent advances in the development of γδ T cell immunotherapy, our understanding of the basic biology of these cells, including how their numbers are regulated in vivo, remains poor. This is particularly true for tissue-resident γδ T cells. We have identified the β2 family of integrins as regulators of γδ T cells. β2-integrin–deficient mice displayed a striking increase in numbers of IL-17–producing Vγ6Vδ1+ γδ T cells in the lungs, uterus, and circulation. Thymic development of this population was normal. However, single-cell RNA sequencing revealed the enrichment of genes associated with T cell survival and proliferation specifically in β2-integrin–deficient IL-17+ cells compared to their wild-type counterparts. Indeed, β2-integrin–deficient Vγ6+ cells from the lungs showed reduced apoptosis ex vivo, suggesting that increased survival contributes to the accumulation of these cells in β2-integrin–deficient tissues. Furthermore, our data revealed an unexpected role for β2 integrins in promoting the thymic development of the IFNγ-producing CD27+ Vγ4+ γδ T cell subset. Together, our data reveal that β2 integrins are important regulators of γδ T cell homeostasis, inhibiting the survival of IL-17–producing Vγ6Vδ1+ cells and promoting the thymic development of the IFNγ-producing Vγ4+ subset. Our study introduces unprecedented mechanisms of control for γδ T cell subsets.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Vicky and Rop, Mr Jesse and McIntyre, Claire and Goodyear, Professor Carl and Otto, Dr Thomas
Authors: McIntyre, C. L., Monin, L., Rop, J. C., Otto, T. D., Goodyear, C. S., Hayday, A. C., and Morrison, V. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:26 August 2020
Copyright Holders:Copyright © 2020 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 117(36):22367-22377
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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