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CD103(+)CD11b(+) Dendritic Cells Induce T(h)17 T Cells in Muc2-Deficient Mice with Extensively Spread Colitis

Journal article
Authors Ulf Alexander Wenzel
Caroline Jonstrand
Gunnar C. Hansson
Mary Jo Wick
Published in Plos One
Volume 10
Issue 6
Pages e0130750
ISSN 1932-6203
Publication year 2015
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages e0130750
Language en
Links dx.doi.org/10.1371/journal.pone.013...
Keywords TUMOR-ASSOCIATED MACROPHAGES, INFLAMMATORY-BOWEL-DISEASE, INTESTINAL, HOMEOSTASIS, LY6C(HI) MONOCYTES, EPITHELIAL-CELLS, IMMUNE CELLS, GUT, DIFFERENTIATION, TOLERANCE, COLON, Multidisciplinary Sciences
Subject categories Microbiology in the medical area, Immunology in the medical area

Abstract

Mucus alterations are a feature of ulcerative colitis (UC) and can drive inflammation by compromising the mucosal barrier to luminal bacteria. The exact pathogenesis of UC remains unclear, but CD4(+) T cells reacting to commensal antigens appear to contribute to pathology. Given the unique capacity of dendritic cells (DCs) to activate naive T cells, colon DCs may activate pathogenic T cells and contribute to disease. Using Muc2(-/-) mice, which lack a functional mucus barrier and develop spontaneous colitis, we show that colitic animals have reduced colon CD103(+)CD11b(-) DCs and increased CD103(-)CD11b(+) phagocytes. Moreover, changes in colonic DC subsets and distinct cytokine patterns distinguish mice with distally localized colitis from mice with colitis spread proximally. Specifically, mice with proximally spread, but not distally contained, colitis have increased IL-1 beta, IL-6, IL-17, TNF alpha, and IFN gamma combined with decreased IL-10 in the distal colon. These individuals also have increased numbers of CD103(+)CD11b(+) DCs in the distal colon. CD103(+)CD11b(+) DCs isolated from colitic but not noncolitic mice induced robust differentiation of Th17 cells but not Th1 cells ex vivo. In contrast, CD103(-)CD11b(+) DCs from colitic Muc2(-/-) mice induced Th17 as well as Th1 differentiation. Thus, the local environment influences the capacity of intestinal DC subsets to induce T cell proliferation and differentiation, with CD103(+)CD11b(+) DCs inducing IL-17-producing T cells being a key feature of extensively spread colitis.

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