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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.
AuthorsHirofumi Yamanishi, Hidehiro Murakami, Yoshiou Ikeda, Masanori Abe, Teru Kumagi, Yoichi Hiasa, Bunzo Matsuura, Morikazu Onji
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 5 Pg. 2164-72 (Mar 01 2012) ISSN: 1550-6606 [Electronic] United States
PMID22291189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Epitopes, T-Lymphocyte
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Carbonic Anhydrase I
Topics
  • Animals
  • CD4-Positive T-Lymphocytes (enzymology, immunology, transplantation)
  • Carbonic Anhydrase I (metabolism, therapeutic use)
  • Cells, Cultured
  • Coculture Techniques
  • Colitis (enzymology, immunology, prevention & control)
  • Dendritic Cells (enzymology, immunology, metabolism)
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte (administration & dosage, immunology)
  • Female
  • Forkhead Transcription Factors (biosynthesis, metabolism)
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit (biosynthesis, deficiency)
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • T-Lymphocytes, Regulatory (cytology, enzymology, immunology)

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