TRR 156:  The skin as sensor and effector orchestrating local and systemic immunity

• Subject Area: Medicine
• Term: since 2015
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

As one of our largest organs, the skin is a vital barrier against environmental pressures and forms, together with the lung and gut, the hosts’ external frontier to the environment. The main challenge in the study of skin immunology is to understand the mechanisms that regulate the cross talk between the various host and microbial cellular components of the skin, and how a perturbation of this communication contributes to altered cutaneous immune responses and to the pathogenesis of inflammatory skin diseases. Also, we are just beginning to understand how skin immune reactions affect – and are affected by - systemic immunity. The goal of this consortium, which is unique in its focus and composition worldwide, is to understand skin immunity in its complexity (as sensor, effector and orchestrator of skin and systemic immune reactions) to generate the basis for future therapies. To achieve this goal, dermatologists, immunologists, microbiologists, pharmacologists and biochemists work together in a unique consortium to gain a better understanding of the complexity of the skin immune system. The second funding period was used to consolidate and concentrate the joint research efforts by especially focussing on the skin microbiome, the interactions between the skin immune system and systemic immunity, as well as by concentrating on inflammatory disease models with a focus on psoriasis. This focus resulted in a considerable number of joint publications that were only made possible by the strong scientific interaction and collaboration within this transregional collaborative research center. It remains the twelve-year-long term vision of TRR156 to study and better understand complex skin immune reactions and to provide translational knowledge for improved therapies for our patients.

• DFG Programme: CRC/Transregios

Current projects

• A01 - Microbiome-host interaction in skin homeostasis and inflammation (Project Heads Peschel, Andreas ;  Schittek, Birgit )
• A02 - Microbiota-dependent expression of IL22 by group 3 innate lymphoid cells regulates skin mesenchymal and epithelial cell differentiation (Project Heads Diefenbach, Andreas ;  Wolz, Christiane )
• B02 - Control of cytotoxic T cell responses in the skin by mononuclear phagocytes during primary viral infection and memory recall (Project Heads Probst, Hans Christian ;  Schild, Hansjörg )
• B03 - The role of neutrophils during induction of tolerance in contact hypersensitivity reactions (Project Head Mahnke, Karsten )
• B04 - Influencing skin inflammation by targeting keratinocyte-T cell interactions and costimulatory signals (Project Head Samstag, Yvonne )
• B05 - Microbe and host RNA-mediated immune activation in the skin (Project Heads Dalpke, Alexander ;  Eigenbrod, Tatjana ;  Hartl, Dominik ;  Weber, Ph.D., Alexander )
• B08 - The role of cellular metabolic pathways and the influence of the microbiome in the pathogenesis of psoriasis (Project Heads Sparwasser, Tim Dominik ;  Vieira-Silva, Ph.D., Sara )
• B09 - Targeting CDK4/6 for the treatment of skin diseases (Project Heads Gehringer, Matthias ;  Hailfinger, Stephan ;  Kramer, Daniela )
• B10 - Microenvironmental control of the Innate Lymphoid Cell reactivity in Contact Hypersensitivity (Project Head Cerwenka, Adelheid )
• B11 - The role of CD18 and regulatory T cells in skin inflammation (Project Heads Bopp, Tobias ;  Grabbe, Stephan )
• C04 - Role of T cell subsets in the pathogenesis of autoimmune blistering disease (Project Heads Enk, Alexander ;  Hadaschik, Eva )
• C05 - Iron regulation and oxidative stress in systemic sclerosis (Project Heads Raker, Verena ;  Schuppan, Detlef ;  Steinbrink, Kerstin )
• C07 - Coagulation receptors in models of cutaneous inflammation (Project Head Ruf, Wolfram )
• C08 - Myeloid cell mediated vascular inflammation in psoriasis (Project Heads Karbach, Susanne Helena ;  Waisman, Ari )
• C09 - Investigating the role of platelets in psoriasis in the context of systemic metabolic inflammation (Project Head Heikenwälder, Mathias )
• C10 - Platelets as novel contributors to psoriasis skin autoinflammation (Project Heads Weber, Ph.D., Alexander ;  Weigelin, Bettina )
• C11 - Immune cell crosstalk in barrier-defective skin driving systemic atopic disease (Project Head Roers, Axel )
• INF - Data management and analysis for skin immunity research (Project Heads Dugas, Martin ;  Heuveline, Vincent )
• KS02 - Defining therapeutic responsiveness in patients with bullous pemphigoid by immunophenotyping (Project Heads Enk, Alexander ;  Kommoss, Katharina ;  Ramcke, Torben )
• Z01 - Central tasks (Project Head Enk, Alexander )
• Z02 - 3D human skin models (Project Head Schittek, Birgit )

Completed projects

• A03 - Orchestrating innate immune responses in leishmaniasis - the role of cutaneous DC subtypes (Project Head von Stebut-Borschitz, Ruth Esther )
• A04 - Innate immune signals and their effect on adaptive hapten-specific immune responses (Project Head Steinbrink, Kerstin )
• A05 - Transcutaneous immunization: Mechanisms of intercellular crosstalk in the skin (Project Heads Radsak, Markus P. ;  Stassen, Michael )
• A06 - Regulation of Th17-mediated skin inflammation by heme oxygenase 1 and inflammasome activation (Project Heads Ghoreschi, Kamran ;  Yazdi, Amir Sadegh )
• A07 - Impact of mast cell activation on T-helper polarization and adaptive immune responses in the skin (Project Heads Feyerabend, Thorsten ;  Rodewald, Hans-Reimer )
• A08 - Consequences of formyl-peptide receptor activation to the skin (Project Head Kretschmer, Dorothee )
• B01 - Functional relevance of the Rho signaling inhibitor Myosin 9B and downstream cytoskeletal proteins for cutaneous dendritic cell populations (Project Heads Bros, Matthias ;  Grabbe, Stephan )
• B06 - The role of ATF3 in linking innate interleukin-1 activation and adaptive type I interferon responses (Project Heads Röcken, Martin ;  Yazdi, Amir Sadegh )
• B07 - Effects of antipsoriatic therapies on aberrant IL-6/STAT3 signaling in psoriasis (Project Heads Eberle, Franziska ;  Ghoreschi, Kamran )
• C01 - Targets and mediators of IL-17 in mouse models of psoriasis and skin infection (Project Heads Kurschus, Ph.D., Florian ;  Waisman, Ari )
• C02 - Immune complex mediated and IgG Fc receptor-dependent recruitment of leukocytes into the skin (Project Heads Olaru, Florina ;  Schäkel, Knut )
• C03 - Impact of noncanonical NF-κB signaling during hapten-induced skin inflammation (Project Heads Kneilling, Manfred ;  Pichler, Bernd )
• C06 - Wnt-associated Dkk3 in inflammatory and fibrosing skin disease (Project Heads Nelson, Peter Jon ;  Sandhoff, Roger )
• KS01 - Clinical Development of imiquimod based immunotherapy (Project Head Radsak, Markus P. )

• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Co-Applicant Institution: Eberhard Karls Universität Tübingen; Johannes Gutenberg-Universität Mainz
• Participating University: Universität Münster
• Participating Institution: Charité - Universitätsmedizin Berlin
• Spokesperson: Professor Dr. Alexander Enk