Increased expression of CCL20 in human inflammatory bowel disease.
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.
Kaser
Arthur
A
Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Innsbruck, Austria.
Ludwiczek
Othmar
O
Holzmann
Sandra
S
Moschen
Alexander R
AR
Weiss
Günter
G
Enrich
Barbara
B
Graziadei
Ivo
I
Dunzendorfer
Stefan
S
Wiedermann
Christian J
CJ
Mürzl
Elisabeth
E
Grasl
Eveline
E
Jasarevic
Zerina
Z
Romani
Nikolaus
N
Offner
Felix A
FA
Tilg
Herbert
H
D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001706:Biopsy; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C121916:CD207 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha