CD301b+ SIRPα+ dendritic cells play a non-redundant role in inducing clonal deletion in the thymus medulla

Abstract

Abstract The thymus contains an assortment of antigen presenting cells (APC) that have distinct locations and antigen processing capabilities. This suggests that they play non-redundant roles in mediating thymocyte selection. Many APC subsets were shown to be capable of driving clonal deletion, however these studies relied primarily on T cell receptor transgenic models. We therefore still do not understand the extent to which distinct APC contribute to clonal deletion in the polyclonal repertoire. Here, we assessed the contribution of different APC subsets to clonal deletion using a cleaved caspase 3-based assay paired with cell type ablation or deficiency. Total deletion frequencies were not altered in the absence of B cells, pDC, or XCR1+ cDC1. In an effort to eliminate SIRPα+ cDC2, we discovered that a substantial proportion of thymic SIRPα+ DC express the lectin CD301b. CD301b+ DCs were localized exclusively within the thymus medulla and depended on IL-4R□. Deficiency of these IL-4/IL-13 signaled DC resulted in a measurable reduction in clonal deletion. These data suggest that CD301b+ SIRPα+ DC represent a distinct population of antigen presenting cells within the thymus and that they are essential for non-redundant deletional tolerance in the polyclonal repertoire.