Integrative tissue biology

Medicine 3

Head of Department:
Prof. Dr. med. univ. Georg Schett

Exploring mechanisms of tissue protection

Head: Dr. med. Stefan Uderhardt

Peripheral tissues are not mere passive recipients of remotely controlled inflammatory responses. Our lab seeks to elucidate the cellular and molecular mechanisms tissues employ in order to protect themselves against unwanted, damaging inflammation. A particular focus of the lab is put on tissue resident macrophages, which - together with interstitial fibroblasts - constitute the universal building blocks of stromal tissues across different organs and even species. Here, we could recently show that RTM are part of a multi-layered regulation of the initial steps of an inflammatory response to tissue damage. We now explore the cellular and molecular biology as well as the mechanistic principles of the anti-inflammatory operations of these phagocytes within the context of a living tissue, and aim to comprehend the reciprocal interactions between resident and recruited immune effector cells on multiple experimental levels. Ultimate goal of our research is to achieve top-down control of complex cellular behavior in intact stromal environment and particularly of the tissue-protective functions of stromal macrophages, in order not only to treat but in fact prevent inflammatory diseases.

  • Wohlfahrt T, Rauber S, Uebe S, Luber M, Soare A, Ekici A, Weber S, Matei AE, Chen CW, Maier C, Karouzakis E, Kiener HP, Pachera E, Dees C, Beyer C, Daniel C, Gelse K, Kremer AE, Naschberger E, Stürzl M, Butter F, Sticherling M, Finotto S, Kreuter A, Kaplan MH, Jüngel A, Gay S, Nutt SL, Boykin DW, Poon GMK, Distler O, Schett G, Distler JHW, Ramming A: PU.1 controls fibroblast polarization and tissue fibrosis. Nature. 2019;():
  • Elhai M, Boubaya M, Distler O, Smith V, Matucci-Cerinic M, Alegre Sancho JJ, Truchetet ME, Braun-Moscovici Y, Iannone F, Novikov PI, Lescoat A, Siegert E, Castellví I, Airó P, Vettori S, De Langhe E, Hachulla E, Erler A, Ananieva L, Krusche M, López-Longo FJ, Distler JHW, Hunzelmann N, Hoffmann-Vold AM, Riccieri V, Hsu VM, Pozzi MR, Ancuta C, Rosato E, Mihai C, Kuwana M, Saketkoo LA, Chizzolini C, Hesselstrand R, Ullman S, Yavuz S, Rednic S, Caimmi C, Bloch-Queyrat C, Allanore Y, for EUSTAR network , Guiducci S, Walker UA, Kyburz D, Lapadula G, Maurer B, Jordan S, Dobrota R, Becvar R, Sierakowsky S, Bielecka OK, Sulli A, Cutolo M, Cuomo G, Nicoara I, Kahan A, Vlachoyiannopoulos PG, Montecucco CM, Caporali R, Stork J, Inanc M, Carreira PE, Novak S, Czirják L, Varju C, Kucharz EJ, Kotulska A, Kopec-Medrek M, Widuchowska M, Cozzi F, Rozman B, Mallia C, Coleiro B, Gabrielli A, Farge D, Wu C, Marjanovic Z, Faivre H, Hij D, Dhamadi R, Wollheim F, Scheja A, Wuttge DM, Andréasson K, Martinovic D, Balbir-Gurman A, Trotta F, Monaco AL, Pellerito R, Mauriziano O, Caramaschi P, Morovic-Vergles J, Black C, Denton C, Damjanov N, Henes J, Santamaria VO, Heitmann S, Krasowska Matthias D, Hasler P, Burkhardt H, Himsel A, Bajocchi G, Pereira Da Silva JA, Salvador MJ, Stamenkovic B, Stankovic A, Selmi CF, Santis M, Tikly M, Denisov LN, Müller-Ladner U, Frerix M, Tarner I, Scorza R, Puppo F, Engelhart M, Strauss G, Nielsen H, Damgaard K, Szucs G, Mendoza AZ, Puente C, Sifuentes Giraldo WA, Midtvedt Ø, Reiseter S, Garen T, Launay D, Valesini G, Ionescu RM, Groseanu L, Opris D, Cornateanu RS, Ionitescu R, Gherghe AM, Soare A, Gorga M, Bojinca M, Milicescu M, Sunderkötter C, Kuhn A, Sandorfi N, Schett G, Beyer C, Meroni P, Ingegnoli F, Mouthon L, Keyser F, Melsens K, Cantatore FP, Corrado A, Iversen L, Mühlen CAV, Bohn JM, Lonzetti LS, Eyerich K, Hein R, Knott E, Wiland P, Szmyrka-Kaczmarek M, Sokolik R, Morgiel E, Madej M, Houssiau FA, Krummel-Lorenz B, Saar P, Aringer M, Günther C, Westhovens R, Lenaerts J, Anic B, Baresic M, Mayer M, Üprus M, Otsa K, Granel B, Müller CS, Radominski SC, Azevedo VF, Jimenez S, Busquets J, Agachi S, Groppa L, Chiaburu L, Russu E, Popa S, Zenone T, Pileckyte M, Mathieu A, Vacca A, Sampaio-Barros PD, Yoshinari NH, Marangoni RG, Martin P, Fuocco L, Stebbings S, Highton J, Chapman P, O'Donnell J, Stamp L, Doube A, Solanki K, Veale D, O'Rourke M, Loyo E, Li M, Abdel Atty Mohamed WA, Amoroso A, Gigante A, Oksel F, Yargucu F, Tanaseanu CM, Popescu M, Dumitrascu A, Tiglea I, Foti R, Chirieac R, Fürst D, Villiger P, Adler S, Laar JV, Kayser C, Fathi N, Hassanien M, de la Pena Lefebvre PG, Rubio SR, Exposito MV, Chatelus E, Sibilia J, Gottenberg JE, Chifflot H, Litinsky I, Emery P, Buch M, Galdo FD, Venalis A, Butrimiene I, Venalis P, Rugiene R, Karpec D, Lasky JA, Cosentino V, Kerzberg E, Montoya F, Bianchi W, Carneiro S, Maretti GB, Bianchi DV, Limonta M, Brucato AL, Lupi E, Rosner I, Rozenbaum M, Slobodin G, Boulman N, Rimar D, Couto M, Kahl S, Chen F, McCloskey D, Malveaux H, Spertini F, Ribi C, Buss G, Martin T, Guffroy A, Poindron V, Chotchaeva F, Mukhin NA, Moiseev S, Herrick A: Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study. Ann Rheum Dis. 2019;78(7): 979-987
  • Sobanski V, Giovannelli J, Allanore Y, Riemekasten G, Airó P, Vettori S, Cozzi F, Distler O, Matucci-Cerinic M, Denton C, Launay D, Hachulla E, EUSTAR collaborators , Cerinic MM, Guiducci S, Walker U, Lapadula G, Iannone F, Becvar R, Sierakowsky S, Cutolo M, Sulli A, Valentini G, Cuomo G, Vettori S, Riemekasten G, Siegert E, Rednic S, Nicoara I, Kahan A, Vlachoyiannopoulos P, Montecucco C, Caporali R, Carreira PE, Novak S, Czirják L, Varju C, Chizzolini C, Kucharz EJ, Kotulska A, Kopec-Medrek M, Widuchowska M, Cozzi F, Rozman B, Mallia C, Coleiro B, Gabrielli A, Farge D, Wu C, Marjanovic Z, Faivre H, Hij D, Dhamadi R, Airó P, Hesselstrand R, Wollheim F, Wuttge DM, Andréasson K, Martinovic D, Balbir-Gurman A, Braun-Moscovici Y, Trotta F, Monaco AL, Hunzelmann N, Pellerito R, Bambara LM, Caramaschi P, Black C, Denton C, Damjanov N, Henes J, Santamaria VO, Heitmann S, Krasowska D, Seidel M, Burkhardt H, Himsel A, Salvador MJ, Da Silva JAP, Stamenkovic B, Stankovic A, Tikly M, Ananieva LP, Denisov LN, Müller-Ladner U, Frerix M, Tarner I, Scorza R, Engelhart M, Strauss G, Nielsen H, Damgaard K, Mendoza AZ, de la Puente C, Sifuentes Giraldo WA, Midtvedt Ø, Reiseter S, Hachulla E, Launay D, Valesini G, Riccieri V, Ionescu RM, Opris D, Groseanu L, Cornateanu RS, Ionitescu R, Gherghe AM, Soare A, Gorga M, Bojinca M, Schett G, Distler JH, Beyer C, Meroni P, Ingegnoli F, Mouthon L, Keyser F, Smith V, Cantatore FP, Corrado A, Pozzi MR, Eyerich K, Hein R, Knott E, Wiland P, Szmyrka-Kaczmarek M, Sokolik R, Morgiel E, Madej M, Krummel-Lorenz B, Saar P, Aringer M, Günther C, Westhovens R, De Langhe E, Lenaerts J, Anic B, Baresic M, Mayer M, Radominski SC, de Souza Müller C, Azevedo VF, Agachi S, Groppa L, Chiaburu L, Russu E, Popa S, Zenone T, Stebbings S, Highton J, Stamp L, Chapman P, O'Donnell J, Solanki K, Doube A, Veale D, O'Rourke M, Loyo E, Li M, Rosato E, Amoroso A, Gigante A, Tanaseanu CM, Popescu M, Dumitrascu A, Tiglea I, Foti R, Chirieac R, Ancuta C, Villiger P, Adler S, de la Pena Lefebvre PG, Rubio SR, Exposito MV, Sibilia J, Chatelus E, Gottenberg JE, Chifflot H, Litinsky I, Venalis A, Butrimiene I, Venalis P, Rugiene R, Karpec D, Saketkoo LA, Lasky JA, Kerzberg E, Montoya F, Cosentino V, Limonta M, Brucato AL, Lupi E, Spertini F, Ribi C, Buss G, Pasquali JL, Martin T, Gorse A: Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis. Arthritis Rheumatol. 2019;71(9): 1553-1570
  • Zehender A, Huang J, Györfi AH, Matei AE, Trinh-Minh T, Xu X, Li YN, Chen CW, Lin J, Dees C, Beyer C, Gelse K, Zhang ZY, Bergmann C, Ramming A, Birchmeier W, Distler O, Schett G, Distler JHW: The tyrosine phosphatase SHP2 controls TGFβ-induced STAT3 signaling to regulate fibroblast activation and fibrosis. Nat Commun. 2018;9(1):
  • Beyer C, Huscher D, Ramming A, Bergmann C, Avouac J, Guiducci S, Meier F, Vettori S, Siegert E, Jaeger VK, Maurer B, Riemekasten G, Walker U, Müller-Ladner U, Valentini G, Matucci-Cerinic M, Allanore Y, Distler O, Schett G, Distler JHW: Elevated serum levels of sonic hedgehog are associated with fibrotic and vascular manifestations in systemic sclerosis. Ann Rheum Dis. 2018;77(4): 626-628
  • Bergmann C, Hallenberger L, Merlevede B, Brandt A, Dees C, Chen CW, Stock M, Beyer C, Distler O, Schett G, Distler J: XIAP AS NOVEL INTEGRATOR OF TGF BETA SIGNALLING AND CANONICAL WNT SIGNALLING IN TISSUE FIBROSIS Ann Rheum Dis. 2018;77(): 739-739
  • Matei AE, Beyer C, Györfi AH, Soare A, Chen CW, Dees C, Bergmann C, Ramming A, Friebe A, Hofmann F, Distler O, Schett G, Distler JHW: Protein kinases G are essential downstream mediators of the antifibrotic effects of sGC stimulators. Ann Rheum Dis. 2018;77(3):
  • Bergmann C, Merlevede B, Beyer C, Hallenberger L, Brandt A, Dees C, Poetter S, Bozec A, Schett G, Distler J: THE AP1 TRANSCRIPTION FACTOR CJUN AMPLIFIES HEDGEHOG-INDUCED FIBROBLAST ACTIVATION AND TISSUE FIBROSIS Ann Rheum Dis. 2018;77(): 732-733
  • Zehender A, Huang J, Gyoerfi AH, Matei AE, Dees C, Beyer C, Gelse K, Ramming A, Bergmann C, Birchmeier W, Distler O, Schett G, Distler J: THE TYROSINE PHOSPHATASE SHP2 CONTROLS TGFB-INDUCED STAT3 SIGNALLING TO REGULATE FIBROBLAST ACTIVATION AND FIBROSIS Ann Rheum Dis. 2018;77(): 733-733
  • Maier C, Ramming A, Bergmann C, Weinkam R, Kittan N, Schett G, Distler JH, Beyer C: Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages. Ann Rheum Dis. 2017;76(6): 1133-1141
 
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Stefan Uderhardt