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Updated: Jan 20, 2026

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes
Published on: June 16, 2011
Mechanism and Regulation of Gasdermin-Mediated Cell Death
Shiyu Xia1, Louis Robert Hollingsworth1, Hao Wu1
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The innate immune system senses and responds to pathogens and endogenous damage through supramolecular protein complexes known as inflammasomes. Cytosolic inflammasome sensor proteins trigger inflammasome assembly on detection of infection and danger. Assembled inflammasomes activate a cascade of inflammatory caspases, which process procytokines and gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that lead to cytokine release and/or programmed lytic cell death, called pyroptosis. In this review, we provide a primer on pyroptosis and focus on its executioner, the GSDM protein family. In addition to inflammasome-mediated GSDMD pore formation, we describe recently discovered GSDMD activation by caspase-8 and elastase in Yersinia-infected macrophages and aging neutrophils, respectively, and GSDME activation by apoptotic caspases. Finally, we discuss strategies that host cells and pathogens use to restrict GSDMD pore formation, in addition to therapeutics targeting the GSDM family.
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