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Dual contribution of the spleen tyrosine kinase (SYK) to epidermolysis bullosa acquisita pathogenesis

Subject Area Dermatology
Term from 2014 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 263860107
 
Final Report Year 2018

Final Report Abstract

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.

Publications

  • 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
    (See online at https://doi.org/10.1016/j.jid.2016.06.619)
  • 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
    (See online at https://doi.org/10.3389/fimmu.2017.00603)
  • 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
    (See online at https://doi.org/10.3389/fimmu.2018.00249)
 
 

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