Kanako Watanabe-Kusunoki, Chenyu Li, Tâmisa Seeko Bandeira Honda, Danyang Zhao, Yoshihiro Kusunoki, John Ku, Hao Long, Martin Klaus, Chao Han, Attila Braun, Elmina Mammadova-Bach, Andreas Linkermann, Kristof Van Avondt, Mathis Richter, Oliver Soehnlein, Monika I Linder, Christoph Klein, Stefanie Steiger, Hans-Joachim Anders
Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure, but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein serving as the final downstream effector of pyroptosis/interleukin (IL)-1pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd-deficiency ameliorated immunothrombosis, acute tissue injury and failure...
April 24, 2024: Blood