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 Otto, Professor Thomas and McIntyre, Claire and Goodyear, Professor Carl |
| 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 > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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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