Expression of the alarmin S100A8 in skin keratinocytes in psoriasis (right) compared to control skin (left).
© J. Roth

    Dermal stress response and barrier integrity in allergy and autoimmune diseases

    The project addresses the role of the pro-inflammatory alarmins S100A8 and S100A9 during dermal inflammation. We have shown that short-term inflammatory activation by S100A8/S100A9 differs significantly from long-term regulatory effects of these proteins. Performing targeted gene editing in immortalized myeloid stem cells we will now investigate which molecular mechanisms and signalling pathways reprogram monocytes and dendritic cells to a regulatory phenotype. We will confirm the relevance of these novel pathways of reprogramming of regulatory myeloid cells in models of dermal inflammation in vivo.

    Research area: Innate immunity, autoimmune diseases

    Prof. Dr. med. Johannes Roth

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Christmann C, Zenker S, Martens L, Hübner J, Loser K, Vogl T, Roth J (2021) Interleukin 17 promotes expression of alarmins S100A8 and S100A9 during the inflammatory response of keratinocytes. Front Immun 11: 599947

      • Pirr S, Dauter L, Vogl T, Ulas T, Bohnhorst B, Roth J, Viemann D (2021) S100A8/A9 is the first predictive marker for neonatal sepsis. Clin Transl Med 11(4):e338

      • Stahl LS, Roth J, Rudack C, McNally A, Weber J, Vogl T, Spiekermann C (2021) Evaluation of the QUANTUM BLUE sCAL rapid test as a point of care tool to identify patients with peritonsillar abscess. Sci Rep 11(1):4497

      • Fischer-Riepe L, Daber NM, Schulte-Schrepping J, Veras de Cavalho BC, Russo A, Pohlen M, Fischer J, Chasan AI, Wolf M, Ulas T, Glander S, Schulz C, Skryabin B, Wollbrink A, Steingraeber N, Stemmel C, Koehler M, Gärtner F, Vettorazzi S, Holzinger D, Gross J, Rosenbauer F, Stoll M, Niemann S, Tuckermann J, Schultze JL, Roth J, Barczyk-Kahlert K. (2020) CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow. J. Allergy Clin. Immunol 146, 1151

      • Leite Dantas R, Bettenworth D, Varga G, Weinhage T, Wami HT, Dobrindt U, Roth J, Vogl T, Ludwig S, Wixler V. (2020) Spontaneous onset of TNFα-triggered colonic inflammation depends on functional T lymphocytes, S100A8/A9 alarmins, and MHC H-2 haplotype. J Pathol 251(4):388-399

      • Li L, Song J, Chuquisana O, Hannocks MJ, Loismann S, Vogl T, Roth J, Hallmann R, Sorokin L (2020) Endothelial Basement Membrane Laminins as an Environmental Cue in Monocyte Differentiation to Macrophages. Front Immunol 11:584229

      • Seethaler A, Stenner M, McNally A, Rudack C, Roth J, Vogl T, Spiekermann C (2020)  IL-8 and IFN-γ as Preoperative Predictors of the Outcome of Tonsillectomy. Ear Nose Throat J 17:145561320910682

      • Skryabin BV, Kummerfeld DM, Gubar L, Seeger B, Kaiser H, Stegemann A, Roth J, Meuth SG, Pavenstädt H, Sherwood J, Pap T, Wedlich-Söldner R, Sunderkötter C, Schwartz YB, Brosius J, Rozhdestvensky TS (2020) Pervasive head-to-tail insertions of DNA templates mask desired CRISPR-Cas9-mediated genome editing events. Sci Adv. 6(7):eaax2941

      • Willers M, Ulas T, Völlger L, Vogl T, Heinemann AS, Pirr S, Pagel J, Fehlhaber B, Halle O, Schöning J, Schreek S, Löber U, Essex M, Hombach P, Graspeuntner S, Basic M, Bleich A, Cloppenborg-Schmidt K, Künzel S, Jonigk D, Rupp J, Hansen G, Förster R, Baines JF, Härtel C, Schultze JL, Forslund SK, Roth J, Viemann D (2020) S100A8 and S100A9 are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants. Gastroenterology 14:S0016-5085(20)35058-7. doi: 10.1053/j.gastro.2020.08.019. Online ahead of print
      • 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.