TRR 241:  Immune-Epithelial Communication in Inflammatory Bowel Diseases

• Subject Area: Medicine ; Biology
• Term: since 2018
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 375876048

Inflammatory bowel diseases (IBD, Crohn’s disease, ulcerative colitis) are characterized by destructive and progressive chronic inflammation of the digestive tract. To date there is no cure available for IBD patients and with the increasing incidence of IBD, there is an urgent clinical need for novel therapies. The lack of curative options stems from the fact, that the early causative events in the etiology of IBD are poorly understood. What is known is that a complex interplay between genetic predisposition, gut microbiota and environmental factors triggers a dysregulated intestinal immune response that initiates and perpetuates mucosal inflammation. Deciphering the molecular and cellular interactions of this interplay and their pathophysiological consequences are the core goals of the TRR 241. A better understanding of IBD mechanisms will create a rationale for future innovative therapeutic approaches. Over the past, researchers in the field of IBD have highlighted two important components in the pathophysiology of IBD, which have been mostly studied in an independent fashion: The epithelial barrier that shields the bowel wall against the intestinal microbiota, and the complex nature of a dense immune cell network and its mediators within the lamina propria. The TRR 241 connects these two components into a concept that highlights the role of immune-epithelial crosstalk in the pathogenesis of IBD and that understands the gut epithelium as an immunological rather than a physical barrier. Thus, the unifying aim of the TRR 241 consortium is to decipher the bidirectional signal exchange between the intestinal epithelium and the mucosal immune system. The TRR 241 hypothesizes that the nature and the spatiotemporal regulation of immune-epithelial communication determine the pathogenesis of IBD. The scientific program of the TRR 241 is classified into three established project areas: In Project Area A, researchers of TRR 241 study how specific cytokines and immune components, released during acute and chronic inflammation within the lamina propria, regulate intestinal barrier function. In Project Area B, involved researchers apply models of barrier dysfunction and antigen exposure to study the temporal and spatial characteristics of developing immune responses. Finally, Project Area C aims to develop and clinically evaluate innovative therapeutic and diagnostic approaches. Collectively, the TRR 241 is highly committed to identifying key mechanisms of immune-epithelial dysregulation and testing new therapeutic targets with the long-term goal of improving the therapy of IBD patients.

• DFG Programme: CRC/Transregios
• International Connection: Austria

Current projects

• A01 - ILC3-myeloid cell crosstalk during homeostatic maintenance of the epithelial barrier and during IBD (Project Heads Diefenbach, Andreas ;  Triantafyllopoulou, Antigoni )
• A02 - Mechanisms linking IFN-mediated mixed lineage kinase domain-like protein activation with intestinal inflammation (Project Head Günther, Claudia )
• A03 - Mucosal immunity as regulator of epithelial cell functions in inflammatory bowel diseases (Project Heads Becker, Christoph ;  Wirtz, Stefan )
• A05 - Oncostatin M as a modulator of pathogenic memory T cells in IBD (Project Head Hegazy, Ph.D., Ahmed Nabil )
• A06 - Molecular mechanisms and therapeutic implications of vascular permeability defects in IBD (Project Heads Britzen-Laurent, Nathalie ;  Stürzl, Michael )
• A07 - The Mevalonate pathway as a checkpoint for regulation of prenylation in intestinal epithelial cells in the context of inflammation (Project Heads Atreya, Ph.D., Imke ;  López Posadas, Ph.D., Rocío )
• A08 - Molecular and functional studies on the crosstalk between induced IELs and IECs in intestinal homeostasis and inflammation (Project Heads Hildner, Kai ;  Neufert, Ph.D., Clemens )
• A09 - Characterizing somatic mutations in immune and epithelial cell communication in ulcerative colitis (Project Heads Sanders, Ashley ;  Weidinger, Carl )
• B01 - Mesenteric fat - an immunological barrier in Crohn's disease? (Project Heads Siegmund, Britta ;  Weidinger, Carl )
• B02 - Signals mediating crosstalk of intestinal epithelial cells with innate lymphoid cells in inflammatory bowel diseases (Project Heads Ludwig, Leif ;  Romagnani, Ph.D., Chiara )
• B03 - Dissecting the role of epithelial inflammasome activation in regulating immune responses in colitis (Project Heads Chang, Hyun-Dong ;  Radbruch, Andreas ;  Ronchi, Francesca )
• B04 - Emergency barriers in Inflammatory Bowel Diseases- Neutrophil-epithelial interplay shapes epithelial restitution in the ulcer microenvironment (Project Heads Herrmann, Martin ;  Koop, Kristina ;  Leppkes, Moritz )
• B05 - Impact of epithelial dysfunction on neuro-immune crosstalk in IBD (Project Heads Becker, Christoph ;  Engel, Matthias ;  Klose, Christoph Siegfried Niki ;  Patankar, Ph.D., Jay )
• B06 - Interplay of the impaired tight junction and the subjacent immune cells in IBD (Project Heads Krug, Susanne Marlen ;  Schulzke, Jörg-Dieter )
• B07 - Dissecting microbial subcellular structures as targets for specific Treg-based therapies (Project Heads Bacher, Petra ;  Scheffold, Alexander )
• B08 - Direct and indirect crosstalk of epithelial GPR15L with immune cells via the intestinal microbiome in the pathogenesis of IBD (Project Head Zundler, Sebastian )
• C01 - Label-free endoscopic analysis of immune-epithelial communication with advanced optical technologies (Project Heads Schürmann, Sebastian ;  Waldner, Ph.D., Maximilian )
• C03 - Transcranial direct current stimulation for chronic, IBD-associated abdominal pain and the relation of pain perception and the intestinal epithelial barrier (Project Heads Atreya, Raja ;  Prüß, Magdalena S. ;  Schumann, Michael )
• C04 - A phase II multi-center clinical trial to study the efficacy and in vivo trafficking of autologous adoptively transferred ex vivo expanded regulatory T cells in patients with ulcerative colitis (Project Heads Bosch-Voskens, Ph.D., Caroline ;  Neurath, Markus F. )
• Z01 - Integrated Research Training Group (iRTG) (Project Heads Atreya, Ph.D., Imke ;  Romagnani, Ph.D., Chiara )
• Z02 - Central Tasks of the Collaborative Research Center (Project Head Becker, Christoph )
• Z03 - IBDome (Project Heads Atreya, Raja ;  Kühl, Anja A. ;  Trajanoski, Zlatko )

Completed projects

• A04 - Microbiota - TLR4 - TNFα axis in control of epithelial tissue functions in IBD (Project Head Kruglov, Andrey A. )
• C02 - Molecular endoscopy to predict response to vedolizumab therapy in ulcerative colitis (Project Heads Atreya, Raja ;  Bojarski, Christian )

• Applicant Institution: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Co-Applicant Institution: Charité - Universitätsmedizin Berlin; Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating Institution: Max-Delbrück-Centrum für Molekulare Medizin (MDC); Berlin Institute of Medical Systems Biology; Bioinformatics Platform; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
• Participating University: Christian-Albrechts-Universität zu Kiel; Medizinische Universität Innsbruck
• Spokesperson: Professor Dr. Christoph Becker