title: Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance.
abstract: Interleukin 10 (IL-10) and regulatory T cells (Tregs) maintain tolerance to intestinal microorganisms. However, Il10(-/-)Rag2(-/-) mice, which lack IL-10 and Tregs, remain healthy, suggesting the existence of other mechanisms of tolerance. Here, we identify suppressor of cytokine signalling 1 (SOCS1) as an essential mediator of immune tolerance in the intestine. Socs1(-/-)Rag2(-/-) mice develop severe colitis, which can be prevented by the reduction of microbiota and the transfer of IL-10-sufficient Tregs. Additionally, we find an essential role for prostaglandin E2 (PGE2) in the maintenance of tolerance within the intestine in the absence of Tregs. Socs1(-/-) dendritic cells are resistant to PGE2-mediated immunosuppression because of dysregulated cytokine signalling. Thus, we propose that SOCS1 and PGE2, potentially interacting together, act as an alternative intestinal tolerance mechanism distinct from IL-10 and Tregs.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Chinen
authors.forename: Kyoko
authors.initials: K
authors.lastname: Komai
authors.forename: Go
authors.initials: G
authors.lastname: Muto
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoue
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D015232:Dinoprostone / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology*; D007213:Indomethacin; D016753:Interleukin-10 / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D015232:Dinoprostone; D007213:Indomethacin