HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ishimaru, N. Articles by Hayashi, Y. PubMed PubMed Citation Articles by Ishimaru, N. Articles by Hayashi, Y.

Development of Inflammatory Bowel Disease in Long-Evans Cinnamon Rats Based on CD4⁺CD25⁺Foxp3⁺ Regulatory T Cell Dysfunction¹

Naozumi Ishimaru^2,*, Akiko Yamada^*, Masayuki Kohashi^*, Rieko Arakaki^*, Tetsuyuki Takahashi, Keisuke Izumi and Yoshio Hayashi^*

^* Department of Oral Molecular Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramotocho, Tokushima, Japan; and Department of Molecular and Environmental Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramotocho, Tokushima, Japan

A mutant strain with defective thymic selection of the Long-Evans Cinnamon (LEC) rat was found to spontaneously develop inflammatory bowel disease (IBD)-like colitis. The secretion of Th1-type cytokines including IFN- and IL-2 from T cells of mesenteric lymph node cells (MLNs) and lamina propria mononuclear cells, but not spleen cells, in LEC rats was significantly increased more than that of the control Long-Evans Agouti rats through up-regulated expression of T-bet and phosphorylation of STAT-1 leading to NF-B activation. In addition, the number of CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells of the thymus, MLNs, and lamina propria mononuclear cells from LEC rats was significantly reduced, comparing with that of the control rats. Moreover, bone marrow cell transfer from LEC rats into irradiated control rats revealed significantly reduced CD25⁺Foxp3⁺ Treg cells in thymus, spleen, and MLNs compared with those from control rats. Indeed, adoptive transfer with T cells of MLNs, not spleen cells, from LEC rats into SCID mice resulted in the development of inflammatory lesions resembling the IBD-like lesions observed in LEC rats. These results indicate that the dysfunction of the regulatory system controlled by Treg cells may play a crucial role in the development of IBD-like lesions through up-regulated T-bet, STAT-1, and NF-B activation of peripheral T cells in LEC rats.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by Grants-in-Aid for Scientific Research (17109016 and 17689049) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

² Address correspondence and reprint requests to Dr. Naozumi Ishimaru, Department of Oral Molecular Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramotocho, Tokushima 770-8504, Japan. E-mail address: ishimaru{at}dent.tokushima-u.ac.jp

³ Abbreviations used in this paper: IBD, inflammatory bowel disease; Treg, regulatory T; DP, double positive; SP, single positive; MLN, mesenteric lymph node cell; LP, lamina propria; BM, bone marrow; PAS, periodic acid Schiff; DAPI, 4',6-diamidino-2-phenylindole; HPRT, hypoxanthine phosphoribosyltransferase; LPMC, LP mononuclear cell.