title: IL-10 downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites.
abstract: Inflammatory bowel disease (IBD) is characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the etiology is poorly understood, it is widely accepted that loss of tolerance is involved in the development of IBD. Therefore, re-establishing tolerance or gut homeostasis is one of the key features in the development of new therapeutic strategies. Here we show that antigen targeting to DEC-205 on dendritic cells leads to an interleukin (IL)-10-dependent downregulation of C-X-C chemokine receptor 3 (CXCR3) expression on differentiated antigen-specific T helper type 1 (Th1) cells in vivo. This downregulation interferes with the migration of Th1 cells into the gut and protects mice against severe acute and relapsing intestinal inflammation. Moreover, CD4(+)CXCR3(+) T cells are highly enriched in the inflamed mucosa of IBD patients. Interference with this pathway may therefore be a promising approach for the treatment of IBD. In conclusion, we propose a hitherto undescribed mechanism by which IL-10 can act on effector T cells and orchestrate intestinal immune responses.
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wadwa
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Klopfleisch
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Adamczyk
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Frede
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Pastille
authors.affiliation: Department of Dermatology, Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Mahnke
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hansen
authors.affiliation: Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Geffers
authors.affiliation: Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: K S
authors.initials: KS
authors.lastname: Lang
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Buer
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Büning
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Westendorf
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002465:Cell Movement; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; C515188:Cxcr3 protein, mouse; C093569:DEC-205 receptor; C556062:IL10 protein, mouse; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface; D016753:Interleukin-10