CCL20 expression is elevated in inflammatory bowel disease and attenuated by vitamin D metabolites

Stallhofer, Johannes ; Reichl, Felix; Lauseker, Michael ; Waldenmaier, Lisa; Török, Helga Paula; Mayerle, Julia ; Olszak, Torsten; Schnitzler, Fabian; Frasheri, Iris ; Breiteneicher, Simone; Brand, Stephan; Stallmach, Andreas ; Diegelmann, Julia und Beigel, Florian (2025): CCL20 expression is elevated in inflammatory bowel disease and attenuated by vitamin D metabolites. In: Scientific Reports, Bd. 15, 20145

Abstract

Intestinal epithelial overexpression of the Th17 cell chemoattractant CCL20 is implicated in inflammatory bowel disease and influenced by NOD2 mutations in Crohn's disease. Vitamin D metabolites have been shown to ameliorate inflammatory bowel disease. Considering NOD2 mutations in Crohn's disease, we investigated whether Vitamin D deficiency (serum 25-hydroxyvitamin D concentration < 20 ng/mL) increases circulating CCL20 levels in inflammatory bowel disease patients and healthy controls and whether active 1,25-dihydroxyvitamin D (calcitriol) downregulates systemic and intestinal CCL20 expression. In a cross-sectional study, serum concentrations of CCL20, 25-hydroxyvitamin D, and calcitriol were measured in 170 NOD2-genotyped Crohn's disease patients, 80 ulcerative colitis patients, and 60 healthy controls. Additionally, the effect of calcitriol on experimentally induced CCL20 expression was examined using human intestinal epithelial HT-29 cells. Multivariable linear regression analyses revealed that both the diagnosis of inflammatory bowel disease and vitamin D deficiency were independently associated with elevated CCL20 levels. Compared to healthy controls, Crohn's disease patients and ulcerative colitis patients exhibited significantly higher circulating CCL20 levels. Unlike in Crohn's disease patients, vitamin D deficiency was associated with higher CCL20 levels in healthy controls and ulcerative colitis patients, whereas the calcitriol/25-hydroxyvitamin D activation ratios were negatively correlated with serum CCL20 levels in healthy controls and ulcerative colitis patients with sufficient serum 25-hydroxyvitamin D status. Furthermore, calcitriol markedly inhibited intestinal epithelial induction of CCL20. In Crohn's disease patients, cholecalciferol supplementation was associated with lower serum CCL20 levels, which were unaffected by NOD2 mutations. These findings suggest that although vitamin D metabolites may downregulate CCL20 expression in healthy controls and ulcerative colitis patients, this regulatory effect appears to be impaired in Crohn's disease patients.

• Dokumententyp: Zeitschriftenartikel
• Keywords: CCL20; Crohn’s disease; C–C motif chemokine ligand 20; Inflammatory bowel disease; Ulcerative colitis; Vitamin D
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie ; Medizin > Klinikum der LMU München > Augenklinik und Poliklinik ; Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik II (Gastroenterologie, Hepatologie) ; Medizin > Klinikum der LMU München > Poliklinik für Zahnerhaltung und Parodontologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2045-2322
• Sprache: Englisch