Interleukin(IL)-7Rα expression regulates murine dendritic cell sensitivity to Thymic Stromal Lymphopoietin

Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-7 are related cytokines that mediate growth and differentiation events in the immune system. They signal through IL-7Rα-containing receptors. Target cells of TSLP in Th2 responses include CD4 T cells and dendritic cells (DC's). While it has been reported that expression of TSLPR on CD4 T cells is required for OVA-induced lung inflammation, DC's have also been shown to be target cells of TSLP. We show here that murine ex vivo splenic DC's are unresponsive to TSLP, as they fail to phosphorylate STAT5, but in vitro overnight culture especially in presence of IL-4 renders DC's responsive to both TSLP and IL-7. This induced responsiveness is accompanied by dramatic upregulation of IL-7Rα on DC's with little change in expression of TSLPR or of γc. In splenic DC's, the induction of IL-7Rα occurs mainly in CD8 negative DC's. In vivo, we found that IL-4 has differential regulatory role on expression of IL-7Rα depending on the cell type; IL-4 decreases IL-7Rα expression on CD4 T cells while upregulating the expression on DC's. Our results indicate that the induction of IL-7Rα expression on DC's is critical for TSLP responsiveness and that IL-4 can upregulate IL-7Rα on DC's.