Wirkung von Signalen des angeborenen Immunsystems auf Hapten-spezifische Immunantworten

    Das Ziel des Projektes ist die Analyse der Interaktion von Mechanismen der angeborenen Immunität mit adaptiven Prozessen bei Allergen/Hapten-spezifischen  Hautreaktionen mit Hilfe der Modelle der Niedrig-Zonen-Toleranz (LZT) und der Contact Hypersensitivity (CHS). Der Schwerpunkt liegt hierbei auf der Bedeutung molekularer (pattern recognition receptors), zellulärer (Myeloide Zellen) und Mikrobiom-vermitttelter Prozesse. Außerdem sollen die im Maussystem erhobenen Daten mit Patientenanalysen verglichen werden, um Schlüsselelemente der angeborenen Immunität als Zielstrukturen neuer Therapieformen für entzündliche Hauterkrankungen zu identifizieren.

    Forschungsgebiet: Immunologie der Haut

    Prof. Dr. Kerstin Steinbrink

    Projektlaufzeit: Juli 2020 - Juni 2024

    • Publikationen

      Originalartikel

      1. Holtkamp CE, Warmus D, Bonowicz K, Gagat M, Linowiecka K, Wolnicka-Glubisz A, Reiter RJ, Böhm M, Slominski AT, Steinbrink K, Kleszczyński K (2023) Ultraviolet radiation-induced mitochondrial disturbances are attenuated by metabolites of melatonin in epidermal keratinocytes. Metabolites 13(7): 861. doi:10.3390/metabo13070861.
      2. Muecklich S, Shehzad K, Tiemann J, Li L, Leson S, Nelson PJ, Jennemann R, Klein M, Becker C, Sandhoff R, Steinbrink K, Raker VK (2023) DKK3 promotes oxidative stress‒induced fibroblast activity. J Invest Dermatol 143(6): 1088-1090.e2.  doi: 10.1016/j.jid.2022.12.004.
      3. Silva Vilches C, Bolduan V, Alabdullah M, Steinbrink K, Prost H C, Enk A, Mahnke K (2023) Topical application of adenosine A2-type receptor agonists prevents contact hypersensitivity reactions in mice by affecting skin dendritic cells. J Invest Dermatol 143(3): 408-418.e6. doi:10.1016/j.jid.2022.07.032.
      4. Yilmaz K, Haeberle S, Kim YO, Fritzler MJ, Weng SY, Goeppert B, Raker VK, Steinbrink K, Schuppan D, Enk A, Hadaschik EN (2023) Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice. Front Immunol 14: 1253649. doi:10.3389/fimmu.2023.1253649.
      5. Fleischer MI, Röhrig N, Raker VK, Springer J, Becker D, Ritz S, Bros M, Stege H, Haist M, Grabbe S, Haub J, Becker C, Reyda S, Disse J, Schmidt T, Mahnke K, Weiler H, Ruf W, Steinbrink K (2022) Protease- and cell type-specific activation of protease-activated receptor 2 in cutaneous inflammation J Thromb Haemost 20(12): 2823-2836.  doi:10.1111/jth.15894.
      6. Grabska-Zielińska S, Pin JM, Kaczmarek-Szczepańska B, Olewnik-Kruszkowska E, Sionkowska A, Monteiro FJ, Steinbrink K, Kleszczyński K (2022) Scaffolds loaded with dialdehyde chitosan and collagen-their physico-chemical properties and biological assessment. Polymers (Basel) 14(9): 1818.  doi:10.3390/polym14091818.
      7. Kaczmarek-Szczepańska B, Pin JM, Zasada L, Sonne MM, Reiter RJ, Slominski AT, Steinbrink K, Kleszczyński K. (2022) Assessment of melatonin-cultured collagen/chitosan scaffolds cross-inked by a glyoxal solution as biomaterials for wound healing. Antioxidants (Basel). 11(3):570. doi:10.3390/antiox11030570
      8. Raker VK, Becker C, Landfester K, Steinbrink K (2020) Targeted Activation of T Cells with IL-2-Coupled Nanoparticles. Cells 9;9(9):2063
      9. Stegemann A, Flis D, Ziolkowski W, Distler JHW, Steinbrink K, Böhm M (2020) The α7 Nicotinic Acetylcholine Receptor: A Promising Target for the Treatment of Fibrotic Skin Disorders. J Invest Dermatol 140(12):2371-2379
      10. Maurer M, Seidel-Guyenot W, Metz M, Knop J, Steinbrink K (2003) Critical role of IL-10 in the induction of low zone tolerance to contact allergens. J Clin Invest 112: 432-439
      11. Seidel-Guyenot W, Perschen S, Dechant N, Alt R, Knop J, Steinbrink K (2006) Low zone tolerance induced by systemic application of allergens inhibits Tc1-mediated skin inflammation. J Allergy Clin Immunol 117:1170-1177
      12. Luckey U, Maurer M, Schmidt T, Lorenz N, Seebach B, Metz M, Steinbrink K (2011) T cell killing by tolerogenic dendritic cells protects mice from allergy. J Clin Invest 121: 3860-3871
      13. Luckey U, Schmidt T, Pfender N, Romer M, Lorenz N, Martin SF, Bopp T, Schmitt E, Nikolaev A, Yogev N, Waisman A, Jakob T, Steinbrink K (2012) Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance. J Allergy Clin Immunol 130: 781-797
      14. Raker VK, Ook KY, Haub J, Lorenz N, Schmidt T, Stegemann A, Böhm M, Schuppan D, Steinbrink K (2016) Myeloid cell populations and fibrogenic parameters in bleomycin- and HOCl-induced fibrosis. Exp Dermatol 25: 887-894
      15. Frick SU, Domogalla MP, Baier G, Wurm FR, Mailaender V, Landfester K, Steinbrink K (2016) IL-2 functionalized nanocapsules for T cell-based immunotherapy. ACS Nano 10: 9216-9226
      16. Schmidt T, Lorenz N, Raker VK, Reißig S, Waisman A, Weigmann B, Steinbrink K (2016) Epicutaneous and oral low zone tolerance protects from colitis in mice. J Invest Dermatol 136: 1831-1839
      17. Kryczanowsky F, Raker V, Graulich E, Domogalla MP, Steinbrink K (2016) IL-10-modulated human human dendritic cells for clinical use: identification of a stable and migratory subset with improved tolerogenic activity. J Immunol 197: 3607-3617
      18. Domogalla MD, Rostan PV, Raker VK, K Steinbrink (2017) Tolerance through education: How tolerogenic dendritic cells shape immunity. Front Immunol 8: 1764
      19. Mahnke K, Useliene J, Ring S, Kage P, Jendrossek V, Robson SC, Bylaite-Bucinskiene M, Steinbrink K, Enk AH (2017) Down-Regulation of CD62L shedding in T cells by CD39+ regulatory T cells leads to defective sensitization in contact hypersensitivity reactions. J Invest Dermatol 137: 106-114
      20. Haeberle S, Raker V, Haub J, Kim YO, Weng SY, Yilmaz OK, Enk A, Steinbrink K*, Schuppan D* Hadaschik EN* (2017) Regulatory T cell deficient-scurfy mice exhibit skin fibrosis and a Th2/M2-like inflammatory response resembling scleroderma. *contributed equally J Dermatol Sci 87: 285-291
      21. Schmidt T, Lorenz N, Raker VK, Schmidgen MI, Mahnke K, Enk A, Roth J, Steinbrink K (2018) Allergen-specific low zone tolerance is independent of MRP8/14-, TLR4-, TLR7-, and TLR9-mediated immune processes. J Invest Dermatol 138: 452-455
      22. Haub J, Roehrig N, Uhrin P, Schabhauer G, Eulberg D, Melchior F, Shahneh F, Probst HC, Becker C, Steinbrink K*, Raker VK*. * contributed equally (2019) Intervention of inflammatory monocyte activity limits dermal fibrosis. J Invest Dermatol 139:2144-2153

       

       

      Reviews

      • Scheib N, Tiemann J, Becker C, Probst HC, Raker VK, Steinbrink K (2022) The dendritic cell dilemma in the skin: Between tolerance and immunity. Front Immunol. 13:929000. doi:10.3389/fimmu.2022.929000
      • Raker VK, Becker C, Landfester K, Steinbrink K (2020) Targeted activation of T cells with IL-2-coupled nanoparticles. Cells. 9(9):2063. doi:10.3390/cells9092063