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: Kenichirou Mori, Hirofumi Yamanishi, Yoshiou Ikeda, Teru Kumagi, Yoichi Hiasa, Bunzo Matsuura, Masanori Abe, Morikazu Onji
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 93 Issue 6 Pg. 963-72 (Jun 2013) ISSN: 1938-3673 [Electronic] United States
• PMID: 23547144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbonic Anhydrase I

Topics

• Administration, Oral
• Animals
• CD4-Positive T-Lymphocytes (immunology, transplantation)
• Carbonic Anhydrase I (administration & dosage, immunology)
• Colitis (immunology, prevention & control)
• Desensitization, Immunologic (methods)
• Disease Models, Animal
• Female
• Flow Cytometry
• Immune Tolerance (immunology)
• Immunohistochemistry
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Real-Time Polymerase Chain Reaction
• T-Lymphocyte Subsets (immunology, transplantation)