Bedeutung der spleen tyrosine kinase (SYK) für die Pathogenese der Epidermolysis bullosa acquisita

• Antragsteller: Professor Dr. Ralf Joachim Ludwig; Unni Krishna Samavedam, Ph.D.
• Fachliche Zuordnung: Dermatologie
• Förderung: Förderung von 2014 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 263860107

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

Collectively we were able to demonstrate that: • Sykb is one of the major hub-genes expressed in the skin of mice with experimental EBA; • pharmacological SYK blockade dose-dependently and almost completely impairs induction of experimental EBA in mice induced by transfer of anti-COL7 IgG; • induction of anti-COL7 IgG-induced EBA requires SYK expression on cells of the myeloid, but not lymphoid linage; • SYK inhibition ablates signaling events downstream of SYK in immune complexactivated neutrophils; • Plaur and Fpr1 are involved in the SYK signaling pathway; • SYK is differentially expressed in skin with pemphigoid disease (BP and EBA) when compared to healthy control skin.

Projektbezogene Publikationen (Auswahl)

• PDE4 inhibition as potential treatment of epidermolysis bullosa acquisita. J Invest Derm (2016) 136:2211-2220
  Koga, Hiroshi; Recke, Andreas; Vidarsson, Gestur; Pas, Hendri H.; Jonkman, Marcel F.; Hashimoto, Takashi; Kasprick, Anika; Ghorbanalipoor, Saeedeh; Tenor, Hermann; Zillikens, Detlef & Ludwig, Ralf J.
  
• Mechanisms of autoantibody-induced pathology. Front Immunol (2017) 8:603
  Ludwig, Ralf J.; Vanhoorelbeke, Karen; Leypoldt, Frank; Kaya, Ziya; Bieber, Katja; McLachlan, Sandra M.; Komorowski, Lars; Luo, Jie; Cabral-Marques, Otavio; Hammers, Christoph M.; Lindstrom, Jon M.; Lamprecht, Peter; Fischer, Andrea; Riemekasten, Gabriela; Tersteeg, Claudia; Sondermann, Peter; Rapoport, Basil; Wandinger, Klaus-Peter; Probst, Christian; ... & Nimmerjahn, Falk
  
• Whole-genome expression profiling in skin reveals SYK as a key regulator of inflammation in experimental epidermolysis bullosa acquisita. Front Immunol (2018) 9:249
  Samavedam, Unni K.; Mitschker, Nina; Kasprick, Anika; Bieber, Katja; Schmidt, Enno; Laskay, Tamás; Recke, Andreas; Goletz, S.; Vidarsson, Gestur; Schulze, Franziska S.; Armbrust, Mikko; Schulze Dieckhoff, Katharina; Pas, Hendri H.; Jonkman, Marcel F.; Kalies, Kathrin; Zillikens, Detlef; Gupta, Yask; Ibrahim, Saleh M. & Ludwig, Ralf J.