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The Journal of Immunology, 2007, 179, 6255 -6262
Copyright © 2007 by The American Association of Immunologists, Inc.

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The Role of Dendritic Cells in the Development of Acute Dextran Sulfate Sodium Colitis1

Bradford E. Berndt*, Min Zhang*, Gwo-Hsiao Chen{dagger}, Gary B. Huffnagle{dagger},{ddagger} and John Y. Kao2,*

* Gastroenterology Division, Department of Internal Medicine, {dagger} Department of Pulmonary and Critical Care Medicine, and {ddagger} Department of Microbiology and Immunology, University of Michigan Health System, Ann Arbor, MI 48109

Dendritic cells (DCs) are essential mediators of the host immune response to surrounding microbes. In this study, we investigate the role of DCs in the pathogenesis of a widely used colitis model, dextran sulfate sodium-induced colitis. The effect of dextran sulfate sodium on the production of proinflammatory cytokines and chemokines by bone marrow-derived DCs (BM-DCs) was analyzed. BM-DCs were adoptively transferred into C57BL/6 mice or DCs were ablated using transgenic CD11c-DTR/GFP mice before treatment with 5% dextran sulfate sodium in drinking water. We found that dextran sulfate sodium induced production of proinflammatory cytokines (IL-12 and TNF-{alpha}) and chemokines (KC, MIP-1{alpha}, MIP-2, and MCP-1) by DCs. Adoptive transfer of BM-DCs exacerbated dextran sulfate sodium colitis while ablation of DCs attenuated the colitis. We conclude that DCs are critical in the development of acute dextran sulfate sodium colitis and may serve a key role in immune balance of the gut mucosa.

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 a Pilot Feasibility grant from the Michigan Gastrointestinal Peptide Research Center (DK-34533) and a grant from the GlaxoSmithKline Institute for Digestive Health.

2 Address correspondence and reprint requests to Dr. John Y. Kao, Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 6520A Medical Science Research Building 1, Special Postal Code 5682, 1150 West Medical Center Drive, Ann Arbor, MI 48109. E-mail address: jykao{at}umich.edu

3 Abbreviations used in this paper: DC, dendritic cell; PMN, polymorphic neutrophil; DSS, dextran sulfate sodium; DT, diphtheria toxin; BM, bone marrow; WT, wild type; CM, complete medium; PMB, polymyxin B; KO, knockout; Tg, transgenic.




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