In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 36 ( 2020-09-08), p. 22367-22377
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 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1921930117
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2020
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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