Indispensable role of IL-10 in the development of antigen cross-presentation capacity of the cDC1 subset

Abstract

Abstract The conventional type 1 dendritic cell (cDC1) is a distinct DC subset with specialized functions including cross-presentation of antigens to CD8 T cells and CD103 expression. cDC1s require GM-CSF signal for gaining their signature functions; however, the involvement of other cytokines remains unknown. Here we found that cDC1s were normal in number but lacked CD103 expression in IL-10-deficient (Il10−/−) mice, suggesting that IL-10 has some effects on cDC1 function in vivo. Thus, next we assessed the CD8 T-cell priming capacity of cDC1s from Il10+/+ and Il10−/− mice by coculture with OT-I CD8+ T cells in the presence of ovalbumin in vitro. In contrast to Il10+/+ cDC1s, Il10−/− cDC1s failed to induce the expansion and IFN-γ production of OT-I cells. In addition, Il10−/− mice had a significantly lower number of memory CD8 T cells in the lymph nodes in the steady state. These results indicate that cDC1s in Il10−/− mice were defective in antigen cross-presentation. We also found that, whereas Flt3-ligand-induced DCs derived from Il10+/+ bone marrow cells upregulated CD103 expression by and CD8 T-cell cross-priming capacity of the cDC1-equivalent population in response to GM-CSF stimulation, Il10−/− bone marrow-derived DCs did not, suggesting that dysfunction of cDC1s in Il10−/− mice is likely due to unresponsiveness to GM-CSF. Finally, we found that mRNA expression of Csf2ra, which encodes GM-CSF receptor α-chain, was completely deficient in both cDC1s in Il10−/− mice and Il10−/− cDC1-equivalent bone marrow-derived DCs. Collectively, our data suggest that IL-10 critically controls the development of antigen cross-presentation capacity of cDC1s under homeostatic conditions, likely through regulating GM-CSF receptor expression.