Regulatory dendritic cells pulsed with carbonic anhydrase I protect mice from colitis induced by CD4+CD25- T cells

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 ident...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2012-03, Vol.188 (5), p.2164-2172
Main Authors: Yamanishi, Hirofumi, Murakami, Hidehiro, Ikeda, Yoshiou, Abe, Masanori, Kumagi, Teru, Hiasa, Yoichi, Matsuura, Bunzo, Onji, Morikazu
Format: Article
Language:English
Subjects:
Animals
Carbonic Anhydrase I - metabolism
Carbonic Anhydrase I - therapeutic use
CD4-Positive T-Lymphocytes - enzymology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - transplantation
Cells, Cultured
Coculture Techniques
Colitis - enzymology
Colitis - immunology
Colitis - prevention & control
Dendritic Cells - enzymology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Disease Models, Animal
Epitopes, T-Lymphocyte - administration & dosage
Epitopes, T-Lymphocyte - immunology
Female
Forkhead Transcription Factors - biosynthesis
Forkhead Transcription Factors - metabolism
Immunophenotyping
Interleukin-2 Receptor alpha Subunit - biosynthesis
Interleukin-2 Receptor alpha Subunit - deficiency
Mice
Mice, Inbred BALB C
Mice, SCID
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - enzymology
T-Lymphocytes, Regulatory - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1100559