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  • 标题:β2 Integrins differentially regulate γδ T cell subset thymic development and peripheral maintenance
  • 本地全文:下载
  • 作者:Claire L. McIntyre ; Leticia Monin ; Jesse C. Rop
  • 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
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