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Critical Role for SLAM/SAP Signaling in the Thymic Developmental Programming of IL-17- and IFN-?-Producing ?? T Cells.

ABSTRACT: During thymic development, mouse ?? T cells commit to either an IFN-?- 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 ?? T cells. Characterization of SLAM family receptor expression revealed that thymic ?? T cell subsets were each marked by distinct coexpression profiles of SLAMF1, SLAMF4, and SLAMF6. In the thymus, V?1 and V?4 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-?-producing ?? T cells, respectively. Disruption of SLAM family receptor signaling through deletion of SAP resulted in impaired thymic V?1 and V?4 T cell maturation at the CD24⁺CD73^-SLAMF1⁺SLAMF6⁺ double positive stage that was associated with a decreased frequency of CD44⁺ROR?t⁺ ?? T cells. Impaired development was in turn associated with decreased ?? T cell IL-17 and IFN-? production in the thymus as well as in peripheral tissues. The role for SAP was subset-specific, as V?1V?6.3, V?4, V?5, but not V?6 subsets were SAP-dependent. Together, these data suggest that the SLAM/SAP signaling pathway plays a larger role in ?? T cell development than previously appreciated and represents a critical checkpoint in the functional programming of both IL-17- and IFN-?-producing ?? T cell subsets.

SUBMITTER: Dienz O

PROVIDER: S-EPMC7065973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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