title: Regulatory dendritic cells pulsed with carbonic anhydrase I protect mice from colitis induced by CD4+CD25- T cells.
abstract: Inflammatory bowel disease (IBD), which is characterized by a dysregulated intestinal immune response, is postulated to be controlled by intestinal self-antigens and bacterial Ags. Fecal extracts called cecal bacterial Ag (CBA) have been implicated in the pathogenesis of IBD. In this study, we identified a major protein of CBA related to the pathogenesis of IBD and established a therapeutic approach using Ag-pulsed regulatory dendritic cells (Reg-DCs). Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, carbonic anhydrase I (CA I) was identified as a major protein of CBA. Next, we induced colitis by transfer of CD4(+)CD25(-) T cells obtained from BALB/c mice into SCID mice. Mice were treated with CBA- or CA I-pulsed Reg-DCs (Reg-DCs(CBA) or Reg-DCs(CA1)), which expressed CD200 receptor 3 and produced high levels of IL-10. Treatment with Reg-DCs(CBA) and Reg-DCs(CA1) ameliorated colitis. This effect was shown to be Ag-specific based on no clinical response of irrelevant Ag (keyhole limpet hemocyanin)-pulsed Reg-DCs. Foxp3 mRNA expression was higher but RORγt mRNA expression was lower in the mesenteric lymph nodes (MLNs) of the Reg-DCs(CA1)-treated mice compared with those in the MLNs of control mice. In the MLNs, Reg-DCs(CA1)-treated mice had higher mRNA expression of IL-10 and TGF-β1 and lower IL-17 mRNA expression and protein production compared with those of control mice. In addition, Reg-DCs(CBA)-treated mice had higher Foxp3(+)CD4(+)CD25(+) and IL-10-producing regulatory T cell frequencies in MLNs. In conclusion, Reg-DCs(CA1) protected progression of colitis induced by CD4(+)CD25(-) T cell transfer in an Ag-specific manner by inducing the differentiation of regulatory T cells.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Tōon, Ehime 791-0295, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamanishi
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Murakami
authors.forename: Yoshiou
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
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: Morikazu
authors.initials: M
authors.lastname: Onji
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000637:transplantation*; D024401:Carbonic Anhydrase I / Q000378:metabolism* / Q000627:therapeutic use; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control*; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000172:deficiency; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000201:enzymology / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D024401:Carbonic Anhydrase I