Lymph node-fibroblastic reticular cells regulate differentiation of CD4+ T cells through CD25

Abstract

Abstract Lymph node-fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impacts of LN-FRCs on naïve CD4+ T cell differentiation have not been explored. Here, we show that FRCs in T cell zones of LNs express CD25 (IL-2 receptor α chain (IL-2Rα) of the IL-2R hetero-trimer). LN-FRCs trans-presented IL-2 to naïve CD4+ T cells through CD25, thereby facilitating early IL-2-mediated signaling. CD25-deficient LN-FRCs attenuated STAT5 phosphorylation of naïve CD4+ T cells during CD4+ T cell lineage differentiation, promoted T helper 17 (Th17) cell differentiation, and induced Th17 immune response-related gene expression. In an experimental autoimmune encephalomyelitis (EAE) disease model, Th17 cell-mediated EAE severity was elevated in mice lacking CD25 in LN-FRCs. Therefore, our results suggest that CD25 expression in LN-FRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring naive CD4+ T cells, influencing immune responses.