Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production

Abstract

The mammalian target of rapamycin (mTOR) controls cell growth and survival through two distinct complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Although several reports have suggested the involvement of mTORC1 in development and function of dendritic cells (DCs), its physiological roles remain obscure. We therefore established mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as RaptorDC−/−). RaptorDC−/− mice exhibited cell expansion in specific subsets of DCs such as splenic CD8+ DCs and intestinal CD11c+CD11b+ DCs. We also found that impaired mTORC1 signal resulted in the suppression of IL-10 production along with enhanced CD86 expression in intestinal CD11c+CD11b+ DCs and that RaptorDC−/− mice were highly susceptible to dextran sodium sulfate-induced colitis. Our results uncover mTORC1-mediated anti-inflammatory programs in intestinal CD11c+CD11b+ DCs to limit the intestinal inflammation.