| First Author | Dienz O | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 6 | Pages | 1521-1534 |
| PubMed ID | 32024701 | Mgi Jnum | J:287500 |
| Mgi Id | MGI:6405864 | Doi | 10.4049/jimmunol.1901082 |
| Citation | Dienz O, et al. (2020) Critical Role for SLAM/SAP Signaling in the Thymic Developmental Programming of IL-17- and IFN-gamma-Producing gammadelta T Cells. J Immunol 204(6):1521-1534 |
| abstractText | During thymic development, mouse gammadelta T cells commit to either an IFN-gamma- or an IL-17-producing phenotype through mechanisms that remain unclear. In this study, we investigated the extent to which the SLAM/SAP signaling pathway regulates the functional programming of gammadelta T cells. Characterization of SLAM family receptor expression revealed that thymic gammadelta T cell subsets were each marked by distinct coexpression profiles of SLAMF1, SLAMF4, and SLAMF6. In the thymus, Vgamma1 and Vgamma4 T cells that exhibited an SLAMF1(+)SLAMF6(+) double positive phenotype were largely contained within immature CD24(+)CD73(-) and CD24(+)CD73(+) subsets, whereas SLAMF1 single positive, SLAMF6 single positive, or SLAMF1SLAMF6 double negative cells were found within mature CD24(-)CD73(+) and CD24(-)CD73(-) subsets. In the periphery, SLAMF1 and SLAMF6 expression distinguished IL-17- and IFN-gamma-producing gammadelta T cells, respectively. Disruption of SLAM family receptor signaling through deletion of SAP resulted in impaired thymic Vgamma1 and Vgamma4 T cell maturation at the CD24(+)CD73(-)SLAMF1(+)SLAMF6(+) double positive stage that was associated with a decreased frequency of CD44(+)RORgammat(+) gammadelta T cells. Impaired development was in turn associated with decreased gammadelta T cell IL-17 and IFN-gamma production in the thymus as well as in peripheral tissues. The role for SAP was subset-specific, as Vgamma1Vdelta6.3, Vgamma4, Vgamma5, but not Vgamma6 subsets were SAP-dependent. Together, these data suggest that the SLAM/SAP signaling pathway plays a larger role in gammadelta T cell development than previously appreciated and represents a critical checkpoint in the functional programming of both IL-17- and IFN-gamma-producing gammadelta T cell subsets. |
