Prof. Dr. Johannes Roth
Functional aspects of alarmins MRP8 (S100A8) and MRP14 (S100A9) in leukocyte migration
Cell Biology / Molecular Biology
Immunology
Vascular Biology / Angiogenesis
Autoimmune Diseases
Influx of leukocytes at sites of inflammation is a hallmark of many diseases. Local factors released during tissue damage or cellular stress called ‚alarmins‘ promote leukocyte recruitment and progression of inflammation. In our group we work on the molecular functions of two novel members of the alarmin family, MRP8 and MRP14, which are released by activated monocytes and granulocytes at local sites of inflammation. Mice deficient for these proteins show altered characteristics in adhesion and transmigration of leukocytes and reduced disease activity under different inflammatory conditions, e. g. in infectious diseases, rheumatoid arthritis or autoimmune diseases. The underlying mechanism, however, is not clear and will be subject of the present proposal. The project comprises the whole methodological spectrum of cell biology, molecular biology, biochemistry and immunology as well as the characterisation of inflammatory processes in animal models of inflammation including in vivo imaging technologies. The final goal is the identification of novel alarmin-dependent inflammatory mechanisms promoting clinically relevant inflammatory diseases.
Vita
- 1988 - 1993: Postdoctoral fellow at the Institute for Experimental Dermatology,
University of Münster - 1993 - 2003: Department of Paediatrics, University of Münster,
Special field ‘Paediatric Immunology and Rheumatology’ - 1999: Board examination for Paediatrics
- 2006: Board examinations for Infectiology and Paediatric Rheumatology
- 2003 - 2008: Professor for Cell Biology, Institute of Experimental Dermatology,
University of Münster - Since 2008: Professor for Immunology, Institute of Immunology, University of Münster
Selected references
Vogt T, Stratis A, Wixler V, Völler T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty D, 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 and Roth J (2018). Auto-inhibitory regulation of S100A8/S100A9-alarmin activity locally restricts sterile inflammation. J. Clin. Invest. 128; 1852-1866.
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 and Viemann D (2017). S100-induced innate immune programming protects newborn infants from sepsis. Nature Immunol. 18; 622-632.
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 and Roth J (2014). Alarmin S100A8/S100A9 as a biomarker of local inflammatory activity. Nature Commun. 5; 4593.
Loser K, Vogl T, Voskort M, Lüken A, Kupas V, Nacken W, Klenner L, Kuhn A, Föll D, Sorokin L, Luger TA, Roth J and Beissert S (2010). The toll-like receptor 4 ligands Mrp8 and Mrp14 play a critical role in the development of autoreactive TCD8+ cells. Nature Med. 6, 713-717.
Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MAD, Nacken W, Foell D, van der Poll T, Sorg C and Roth J (2007). MRP8 and MRP14 are novel endogenous activators of toll-like receptor 4 promoting lethal endotoxin-induced shock.Nature Med. 13, 1042-1049.
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