title: Proteomic analysis of the inflamed intestinal mucosa reveals distinctive immune response profiles in Crohn's disease and ulcerative colitis.
abstract: Although Crohn's disease (CrD) and ulcerative colitis (UC) share several clinical features, the mechanisms of tissue injury differ. Because the global cellular function depends upon the protein network environment as a whole, we explored changes in the distribution and association of mucosal proteins to define key events involved in disease pathogenesis. Endoscopic biopsies were taken from CrD, UC, and control colonic mucosa, and Multi-Epitope-Ligand-Cartographie immunofluorescence microscopy with 32 different Abs was performed. Multi-Epitope-Ligand-Cartographie is a novel, highly multiplexed robotic imaging technology which allows integrating cell biology and biomathematical tools to visualize dozens of proteins simultaneously in a structurally intact cell or tissue. In CrD, the number of CD3+CD45RA+ naive T cells was markedly increased, but only activated memory, but not naive, T cells expressed decreased levels of Bax, active caspase-3 or -8. In UC, only CD4+ T cells coexpressing NF-kappaB were caspase-8 and poly(ADP-ribose)-polymerase positive. Furthermore, the number of CD4+CD25+ T cells was elevated only in UC, whereas in CrD and controls, the number of these cells was similar. By using hub analysis, we also identified that the colocalization pattern with NF-kappaB+ and poly(ADP-ribose)-polymerase+ as base motifs distinguished CrD from UC. High-content proteomic analysis of the intestinal mucosa demonstrated for the first time that different T cell populations within the intestinal mucosa express proteins translating distinct biological functions in each form of inflammatory bowel disease. Thus, topological proteomic analysis may help to unravel the pathogenesis of inflammatory bowel disease by defining distinct immunopathogenic profiles in CrD and UC.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Charité-Campus Virchow Clinic, Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Berndt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bartsch
authors.forename: Lars
authors.initials: L
authors.lastname: Philipsen
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Axel U
authors.initials: AU
authors.lastname: Dignass
authors.forename: Marcus
authors.initials: M
authors.lastname: Hämmerle
authors.forename: Andreas
authors.initials: A
authors.lastname: Sturm
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002449:Cell Aggregation / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D020650:Combinatorial Chemistry Techniques; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000096:biosynthesis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D006680:HLA Antigens; D020543:Proteome