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 H, Recke A, Vidarsson G, Pas HH, Jonkman MF, Hashimoto T, Kasprick A, Ghorbanalipoor S, Tenor H, Zillikens D, Ludwig RJ
  
• Mechanisms of autoantibody-induced pathology. Front Immunol (2017) 8:603
  Ludwig RJ, Vanhoorelbeke K, Leypoldt F, Kaya K, Bieber K, McLachlan SM, Komorowski L, Luo J, Cabral-Marques O, Hammers CM, Lindstrom JM, Lamprecht P, Fischer A, Riemekasten G, Tersteeg C, Sondermann P, Rapoport B, Wandinger K-P, Probst C, El Beidaq A, Schmidt E, Verkman A, Manz RA, Nimmerjahn F
  
• 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 UK, Mitschker N, Kasprick K, Bieber K, Schmidt E, Laskay T, Recke A, Vidarsson G, Schulze FS, Armbrust M Schulze Dieckhoff K, Pas HH, Jonkman M, Kalies K, Zillikens D, Gupta Y, Ibrahim S, Ludwig RJ