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.
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Authors | Hirofumi Yamanishi, Hidehiro Murakami, Yoshiou Ikeda, Masanori Abe, Teru Kumagi, Yoichi Hiasa, Bunzo Matsuura, Morikazu Onji |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 188
Issue 5
Pg. 2164-72
(Mar 01 2012)
ISSN: 1550-6606 [Electronic] United States |
PMID | 22291189
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Epitopes, T-Lymphocyte
- Forkhead Transcription Factors
- Foxp3 protein, mouse
- Il2ra protein, mouse
- Interleukin-2 Receptor alpha Subunit
- Carbonic Anhydrase I
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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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