?2 Integrins differentially regulate ?? T cell subset thymic development and peripheral maintenance.

ABSTRACT: The ?? 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 ?? 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 ?? T cells. We have identified the ?₂ family of integrins as regulators of ?? T cells. ?₂-integrin-deficient mice displayed a striking increase in numbers of IL-17-producing V?6V?1⁺ ?? 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 ?₂-integrin-deficient IL-17⁺ cells compared to their wild-type counterparts. Indeed, ?₂-integrin-deficient V?6⁺ cells from the lungs showed reduced apoptosis ex vivo, suggesting that increased survival contributes to the accumulation of these cells in ?₂-integrin-deficient tissues. Furthermore, our data revealed an unexpected role for ?₂ integrins in promoting the thymic development of the IFN?-producing CD27⁺ V?4⁺ ?? T cell subset. Together, our data reveal that ?₂ integrins are important regulators of ?? T cell homeostasis, inhibiting the survival of IL-17-producing V?6V?1⁺ cells and promoting the thymic development of the IFN?-producing V?4⁺ subset. Our study introduces unprecedented mechanisms of control for ?? T cell subsets.

SUBMITTER: McIntyre CL 

PROVIDER: S-EPMC7486781 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature