Epidermal stress response and barrier integrity in allergy and autoimmune diseases

    The skin is one of the main immunological barriers sensing many different triggers from external microorganisms and tissue-derived signals. The goal of our research project is to analyse the S100-alarmin driven stress response during dermal inflammation in autoimmune diseases and allergies. We will analyse the time-, dose- and tissue-dependent effects of S100A8 and S100A9 on a molecular level with respect to their activating and regulatory functions on the skin immune system. Our approach will define new regulatory mechanisms of dermal inflammation which may point to novel molecular targets for future therapies.

    Research area: Innate immunity, autoimmune diseases

    Prof. Dr. med. Johannes Roth

    Funding period: July 2012 - June 2020

    • Publications

      Original articles

      • Freise N, Burghard A, Ortkras T, Daber N, Chasan AI, Jauch S, Fehler O, Hillebrand J, Schakaki M, Rojas J, Grimbacher B, Vogl T, Hoffmeier A, Martens S, Roth J, Austermann J (2019) Regulatory signaling mechanisms of phagocyte re-programming during systemic vascular inflammation. Blood 134:134-146.
      • Masthoff M, Gran S, Zhang X, Wachsmuth L, Bietenbeck M, Helfen A, Heindel W, Sorokin L, Roth J, Eisenblätter M, Wildgruber M, Faber C (2019) Temporal window for detection of inflammatory disease using dynamic cell tracking with time-lapse MRI. Scientific Rep. 8:9563.
      • Gran S, Honold L, Fehler O, Zenker S, Eligehausen S, Kuhlmann MT, Greven E, van den Bosch M, van Lent P, Spiekermann C, Hermann S, Vogl T, Schäfers M, Roth J (2018) Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment in vivo. Theranostics 8:2407-2423.
      • Heming MO, Gran S, Klotz L, Hermann S, Schäfers M, Roth J, Barczyk-Kahlert K (2018). PPAR-gamma Modulates the Response of Macrophages to Lipopolysaccharide and Glucocorticoids. Frontiers in Immunology, 9, 893.
      • Vogl T, Stratis A, Wixler V, Völler T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty DD, Fröhling M, Paruzel P, Wehmeyer C, Hermann S, Papantonopoulou O, Geyer C, Loser K, Schäfers M, Ludwig S, Stoll M, Leanderson T, Schultze JL, König S, Pap T, Roth J (2018) Auto-inhibitory regulation of S100A8/S100A9-alarmin activity locally restricts sterile inflammation.  J. Clin. Invest. 128:1852-1866
      • Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper M, Blower P, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T, Ng T (2017) Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7:2392-2401.
      • Ulas T, Pirr S, Fehlhaber B, Bickes M, Loof TG, Vogl T, Mellinger L, Heinemann AS, Burgmann J, Schöning J, Schreek S, Pfeifer S, Reuner F, Völlger L, Stanulla M, von Köckritz-Blickwede M, Glander S, Barczyk-Kahlert K, von Kaisenberg CS, Friesenhagen J, Fischer-Riepe L, Zenker S, Schultze JL, Roth J, Viemann S (2017) S100-induced innate immune programming protects newborn infants from sepsis. Nature Immunol. 18:622-632..
      • Fassl SK, Austermann J, Papantonopoulou O, Riemenschneider M, Xue J, Bertheloot D, Freise N, Spiekermann C, Witten A, Viemann D, Kirschnek S, Stoll M, Latz E, Schultze JL, Roth J, Vogl T (2015) Transcriptome assessment reveals a dominant role for TLR4 in the activation of human phagocytes by the alarmin MRP8. J Immunol 194: 575-583. (doi/10.4049/jimmunol.1401085.) 
      • Holzinger D, Fassl SK, de Jager W, Lohse P, Rohrig UF, Gattorno M, Omenetti A, Chiesa S, Schena F, Austermann J, Vogl T, Kuhns DB, Holland SM, Rodriguez-Gallego C, Lopez-Almaraz R, Arostegui JI, Colino E, Roldan R, Fessatou S, Isidor B, Poignant S, Ito K, Epple HJ, Bernstein JA, Jeng M, Frankovich J, Lionetti G, Church JA, Ong PY, LaPlant M, Abinun M, Skinner R, Bigley V, Sachs UJ, Hinze C, Hoppenreijs E, Ehrchen J, Foell D, Chae JJ, Ombrello A, Aksentijevich I, Sunderkoetter C, Roth J (2015) Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases. J Allergy Clin Immunol 136: 1337-1345.
      • Wache C, Klein M, Ostergaard C, Angele B, Häcker H, Pfister H-W, Pruenster M, Sperandio M, Leanderson T, Roth J, Vogl T, Koedel U (2015) Myeloid-related protein 14 promote inflammation and injury in meningitis. J Infect Dis (in press).  (pii: jiv028. Epub ahead of print)
      • Austermann J, Friesenhagen J, Fassl SK, Ortkras T, Burgmann J, Barczyk-Kahlert K, Faist E, Zedler S, Pirr S, Rohde C, Müller-Tidow C, von Köckritz-Blickwede M, von Kaisenberg CS, Flohé SB, Ulas T, Schultze JL, Roth J, Vogl T , Viemann D (2014) Alarmins MRP8 and MRP14 induce stress-tolerance in phagocytes under sterile inflammatory conditions. Cell Rep 9: 2112-2123. (doi/10.1016/j.celrep.2014.11.020)
      • Holzinger D, Nippe N, Vogl T, Marketon K, Mysore V, Weinhage T, Dalbeth N, Pool B, Merriman T, Baeten D, Ives A, Busso N, Foell D, Bas S, Gabay C, Roth J (2014) Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout. Arthritis Rheumatol 66: 1327-1339.
      • Vogl T, Eisenblätter M, Völler T, Zenker S, Hermann S, van Lent P, Faust A, Geyer C, Petersen B, Roebrock K, Schäfers M, Bremer C, Roth J (2014) Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 5: 4593. (doi: 10.1038/ncomms5593)
      • Foell D, Wittkowski H, Kessel C, Lüken A, Weinhage T, Varga G, Vogl T, Wirth T, Viemann D, Björk P, van Zoelen MAD, Gohar F, Srikrishna G, Kraft M, Roth J (2013) Pro-inflammatory S100A12 can activate human monocytes via Toll-like Receptor 4. Am J Respir Crit Care Med 187: 1324-1334.
      • Petersen B, Wolf M, Austermann J, van Lent PLEM, Foell D, Ahlmann M, Kupas V, Loser K, Sorg C, Roth J, Vogl T (2013) The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis. EMBO J 32: 100-111.