title: 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 Raptor(DC-/-)). Raptor(DC-/-) 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 Raptor(DC-/-) 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.
authors.affiliation: Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohtani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshii
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046912:Multiprotein Complexes; D011506:Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018845:CD11 Antigens; D039481:CD11b Antigen; D046912:Multiprotein Complexes; D011506:Proteins; D016753:Interleukin-10; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases