Increased expression of CCL20 in human inflammatory bowel disease

Arthur Kaser; Othmar Ludwiczek; Sandra Holzmann; Alexander R Moschen; Günter Weiss; Barbara Enrich; Ivo Graziadei; Stefan Dunzendorfer; Christian J Wiedermann; Elisabeth Mürzl; Eveline Grasl; Zerina Jasarevic; Nikolaus Romani; Felix A Offner; Herbert Tilg

doi:10.1023/B:JOCI.0000018066.46279.6b

Increased expression of CCL20 in human inflammatory bowel disease

J Clin Immunol. 2004 Jan;24(1):74-85. doi: 10.1023/B:JOCI.0000018066.46279.6b.

Authors

Arthur Kaser¹, Othmar Ludwiczek, Sandra Holzmann, Alexander R Moschen, Günter Weiss, Barbara Enrich, Ivo Graziadei, Stefan Dunzendorfer, Christian J Wiedermann, Elisabeth Mürzl, Eveline Grasl, Zerina Jasarevic, Nikolaus Romani, Felix A Offner, Herbert Tilg

Affiliation

¹ Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Innsbruck, Austria.

PMID: 14997037
DOI: 10.1023/B:JOCI.0000018066.46279.6b

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

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies / immunology
Antibodies / metabolism
Antigens, CD
Antigens, Surface / immunology
Antigens, Surface / metabolism
Biopsy
Chemokine CCL20
Chemokines, CC / genetics
Chemokines, CC / immunology*
Chemokines, CC / metabolism
Colitis, Ulcerative / genetics
Colitis, Ulcerative / immunology*
Colitis, Ulcerative / metabolism
Colitis, Ulcerative / pathology
Crohn Disease / genetics
Crohn Disease / immunology*
Crohn Disease / metabolism
Crohn Disease / pathology
Dendritic Cells / immunology
Dendritic Cells / metabolism
Epithelium / immunology
Epithelium / metabolism
Epithelium / pathology
Female
Humans
Lectins, C-Type / immunology
Lectins, C-Type / metabolism
Macrophage Inflammatory Proteins / genetics
Macrophage Inflammatory Proteins / immunology*
Macrophage Inflammatory Proteins / metabolism
Male
Mannose-Binding Lectins / immunology
Mannose-Binding Lectins / metabolism
Middle Aged
RNA, Messenger / metabolism
Receptors, CCR6
Receptors, Chemokine / immunology
Receptors, Chemokine / metabolism
Tumor Necrosis Factor-alpha / immunology
Tumor Necrosis Factor-alpha / metabolism

Substances

Antibodies
Antigens, CD
Antigens, Surface
CCL20 protein, human
CCR6 protein, human
CD207 protein, human
Chemokine CCL20
Chemokines, CC
Lectins, C-Type
Macrophage Inflammatory Proteins
Mannose-Binding Lectins
RNA, Messenger
Receptors, CCR6
Receptors, Chemokine
Tumor Necrosis Factor-alpha