| First Author | McIntyre CL | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 36 | Pages | 22367-22377 |
| PubMed ID | 32848068 | Mgi Jnum | J:296015 |
| Mgi Id | MGI:6455831 | Doi | 10.1073/pnas.1921930117 |
| Citation | McIntyre CL, et al. (2020) beta2 Integrins differentially regulate gammadelta T cell subset thymic development and peripheral maintenance. Proc Natl Acad Sci U S A 117(36):22367-22377 |
| abstractText | The gammadelta 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 gammadelta 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 gammadelta T cells. We have identified the beta2 family of integrins as regulators of gammadelta T cells. beta2-integrin-deficient mice displayed a striking increase in numbers of IL-17-producing Vgamma6Vdelta1(+) gammadelta 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 beta2-integrin-deficient IL-17(+) cells compared to their wild-type counterparts. Indeed, beta2-integrin-deficient Vgamma6(+) cells from the lungs showed reduced apoptosis ex vivo, suggesting that increased survival contributes to the accumulation of these cells in beta2-integrin-deficient tissues. Furthermore, our data revealed an unexpected role for beta2 integrins in promoting the thymic development of the IFNgamma-producing CD27(+) Vgamma4(+) gammadelta T cell subset. Together, our data reveal that beta2 integrins are important regulators of gammadelta T cell homeostasis, inhibiting the survival of IL-17-producing Vgamma6Vdelta1(+) cells and promoting the thymic development of the IFNgamma-producing Vgamma4(+) subset. Our study introduces unprecedented mechanisms of control for gammadelta T cell subsets. |
