IL-10 mediated immunosuppression: March-I induction regulates antigen presentation by macrophages but not dendritic cells [Immunology]

September 25th, 2015 by Mittal, S. K., Cho, K.-J., Ishido, S., Roche, P. A.

Efficient immune responses require regulated antigen presentation to CD4 T cells. IL-10 inhibits the ability of DCs and macrophages to stimulate antigen-specific CD4 T cells, however the mechanisms by which IL-10 suppresses antigen presentation remain poorly understood. We now report that IL-10 stimulates expression of the E3 ubiquitin-ligase March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in DCs, does not suppress MHC-II or CD86 expression on either resting or activated DCs, and does not affect antigen presentation by activated DCs. IL-10 does, however, inhibit the process of DC activation itself, thereby reducing the efficiency of antigen presentation in a March-I-independent manner. Thus, IL-10 suppression of APC function in macrophages is March-I-dependent whereas in DCs suppression is March-I-independent.