Abstract
Inflammatory bowel disease (IBD) constituting Crohn's disease (CD) and ulcerative colitis (UC) is related to a dysregulated T cell response. CCL20 attracts memory T lymphocytes and dendritic cells. We asked whether CCL20 expression is altered in IBD. Colonic biopsies were obtained from 114 subjects with IBD, non-IBD colitis, irritable bowel syndrome, and healthy controls. CCL20 and CCR6 mRNA expression was measured by Taqman-PCR, and protein secretion from colonic explant cultures (CEC) and its regulation by TNF-alpha by ELISA. CCL20, CCR6, and Langerin were identified by immunohistochemistry and immunofluorescence. CCL20 mRNA and protein were severalfold increased in involved CD and UC but not in non-IBD colitis. TNF-alpha increased and anti-TNF-alpha decreased CCL20 release in healthy control CEC but not in involved IBD colonic specimens. CCL20 localized to follicle-associated epithelium, and CCR6 to the adjacent mantle zone of lymphoid follicles. Furthermore, abundant numbers of Langerin(+) immature dendritic cells were identified in the subepithelial space of IBD specimens. CCL20 might regulate the attraction of T lymphocytes and dendritic cells in IBD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antibodies / immunology
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Antibodies / metabolism
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Antigens, CD
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Antigens, Surface / immunology
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Antigens, Surface / metabolism
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Biopsy
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Chemokine CCL20
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Chemokines, CC / genetics
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Chemokines, CC / immunology*
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Chemokines, CC / metabolism
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Colitis, Ulcerative / genetics
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Colitis, Ulcerative / immunology*
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Colitis, Ulcerative / metabolism
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Colitis, Ulcerative / pathology
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Crohn Disease / genetics
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Crohn Disease / immunology*
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Crohn Disease / metabolism
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Crohn Disease / pathology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Epithelium / immunology
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Epithelium / metabolism
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Epithelium / pathology
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Female
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Humans
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology*
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Macrophage Inflammatory Proteins / metabolism
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Male
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Mannose-Binding Lectins / immunology
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Mannose-Binding Lectins / metabolism
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Middle Aged
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RNA, Messenger / metabolism
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Receptors, CCR6
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Receptors, Chemokine / immunology
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Receptors, Chemokine / metabolism
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antibodies
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Antigens, CD
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Antigens, Surface
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CCL20 protein, human
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CCR6 protein, human
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CD207 protein, human
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Chemokine CCL20
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Chemokines, CC
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Lectins, C-Type
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Macrophage Inflammatory Proteins
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Mannose-Binding Lectins
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RNA, Messenger
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Receptors, CCR6
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Receptors, Chemokine
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Tumor Necrosis Factor-alpha