CD103+ CD11b+ Dendritic Cells Induce Th17 T Cells in Muc2-Deficient Mice with Extensively Spread Colitis

• Published in: PloS one Vol. 10; no. 6; p. e0130750
• Main Authors: Wenzel, Ulf A, Jonstrand, Caroline, Hansson, Gunnar C, Wick, Mary Jo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.06.2015; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Antigens, CD - metabolism; Biochemistry; CD103 antigen; CD11 Antigens - metabolism; CD11b antigen; CD11b Antigen - metabolism; CD4 antigen; Cell Count; Cell Proliferation; Colitis - immunology; Colitis - pathology; Colon; Colon - pathology; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Differentiation; Helper cells; Homeostasis; Immunology; Inflammation; Inflammation Mediators - metabolism; Inflammatory bowel disease; Integrin alpha Chains - metabolism; Interleukin 10; Interleukin 17; Interleukin 6; Intestine; Lymphocyte Subsets - immunology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mucin-2 - deficiency; Mucin-2 - metabolism; Mucosa; Mucus; Neutrophils; Neutrophils - metabolism; Pathogenesis; Phagocytes; Rectum - pathology; Rodents; Th17 Cells - immunology; Tumor necrosis factor-α; Ulcerative colitis; γ-Interferon; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130750

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-1β, IL-6, IL-17, TNFα, and IFNγ 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.