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Immunobiology of Dendritic Cells in Inflammatory Bowel Disease

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Crohn's Disease and Ulcerative Colitis

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Abstract

Breakdown of immunological tolerance toward the commensal microflora in genetically susceptible individuals is believed to be the key event in the pathogenesis of inflammatory bowel disease. Dendritic cells (DC) control the critical balance between anergy and immunity due to their functional dichotomy of being either the most potent antigen presenters or effective inducers of (peripheral) tolerance. Due to their expression of the entire spectrum of pattern recognition receptors (PRRs), such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain NOD they can sense virtually all microbial-associated molecular patterns (MAMPs). This puts them in a pivotal position for understanding the distinct innate and adaptive immune responses intestinal microbiota induce in inflammatory bowel disease.

Peripheral blood and mucosal myeloid dendritic cells from Crohn’s and ulcerative colitis patients express TLR2, TLR4, and NOD. Myeloid DC in IBD are important producers and secretors of key inflammatory cytokines such as IL-1, IL-6, IL-8, IL-12, IL-17, IL-23, IL-27, TNF-α, and nitric oxide depending on their location. Single-nucleotide polymorphisms in the TLR4 receptor have been associated with Crohn’s disease and strongly polarize Th1 responses against commensal microorganisms by TLR4 mutant DC from Crohn’s patients. NOD2 and ATG16L1 mutant DC from individuals with Crohn’s disease are defective in autophagy induction, required for both bacterial handling and antigen-specific CD4+ T-cell responses.

The peripheral blood circulating fraction of dendritic cells correlates with disease activity. DC in IBD were shown to express intercellular adhesion molecule-1 (ICAM-1), integrin α4β7 (CD49d), CCR6, CCR7 (CD197) that facilitate their migration and retention in the mucosal and mesenteric lymph node spaces. Secretion of CCL21 by stromal cells and high endothelial venules (HEV) attracts them to and retains them in mesenteric lymph nodes. Here they secrete CCL19 that increases their own CCR7 expression also attract CCR9+ α4β7+ T lymphocytes. Their expression of CXCR13 probably attracts B cells.

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  1. Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical Center – Virchow Hospital, Medical School of the Humboldt-University of Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Daniel C. Baumgart MD, PhD

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    Daniel C. Baumgart

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Baumgart, D.C. (2012). Immunobiology of Dendritic Cells in Inflammatory Bowel Disease. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0998-4_10

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