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* Division of Gastroenterology and Hepatology, Department of Medicine, Charité–Campus Virchow Clinic, Universitätsmedizin Berlin, Berlin, Germany;
MelTec, Magdeburg, Germany; and
Division of Gastroenterology, Istituti di Ricovero e Cura a Carattere Scientifico Istituto Clinico Humanitas, Rozzano, Milan, Italy
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-
B 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-B+ 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was financially supported by the Charité Medical School (Berlin, Germany).
2 U.B. and S.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Andreas Sturm, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mail address: andreas.sturm{at}charite.de
4 Abbreviations used in this paper: CrD, Crohn’s disease; UC, ulcerative colitis; IBD, inflammatory bowel disease; MELC, Multi-Epitope-Ligand-Carthographie; CMP, combinatorial molecular phenotype; PARP, poly(ADP-ribose)-polymerase; IHC, immunohistochemistry; BW, bodyweight.
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