期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：36
页码：22367-22377
DOI：10.1073/pnas.1921930117
出版社：The National Academy of Sciences of the United States of America
摘要：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 β 2 family of integrins as regulators of γδ T cells. β 2 -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 β 2 -integrin–deficient IL-17 cells compared to their wild-type counterparts. Indeed, β 2 -integrin–deficient Vγ6 cells from the lungs showed reduced apoptosis ex vivo, suggesting that increased survival contributes to the accumulation of these cells in β 2 -integrin–deficient tissues. Furthermore, our data revealed an unexpected role for β 2 integrins in promoting the thymic development of the IFNγ-producing CD27 Vγ4 γδ T cell subset. Together, our data reveal that β 2 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.
关键词：β2 integrins ; γδ T cells ; immune homeostasis
