title: Oral administration of carbonic anhydrase I ameliorates murine experimental colitis induced by Foxp3-CD4+CD25- T cells.
abstract: IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-β production in the MLN and colon; had lower RORγt mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Kenichirou
authors.initials: K
authors.lastname: Mori
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamanishi
authors.forename: Yoshiou
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Teru
authors.initials: T
authors.lastname: Kumagi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.forename: Bunzo
authors.initials: B
authors.lastname: Matsuura
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D024401:Carbonic Anhydrase I / Q000008:administration & dosage* / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000517:prevention & control; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
chemical_list: D024401:Carbonic Anhydrase I
keywords: CD103+ dendritic cell; aldehyde dehydrogenase family 1a2; inflammatory bowel disease; regulatory T cell; tolerance