New insights into the noncanonical inflammasome point to caspase-4 as a druggable target

IF 67.7 1区医学 Q1 IMMUNOLOGY

Nature Reviews Immunology Pub Date : 2025-03-05 DOI:10.1038/s41577-025-01142-9

Elad Elkayam, Francois G. Gervais, Hao Wu, Michael A. Crackower, Judy Lieberman

引用次数: 0

Abstract

Recent studies indicate that the human lipopolysaccharide sensor caspase-4, unlike its mouse homologue caspase-11, is constitutively expressed and activates pro-IL-18 as well as gasdermin D-mediated pyroptosis. Activation of human caspase-4 causes vascular leakage systemically and at the blood–brain barrier in mice and is implicated in the pathogenesis of a range of inflammatory diseases for which there are currently no effective therapies. These results suggest the therapeutic potential of modulating caspase-4 activity, and structural studies indicate that the caspase-4 exosite might be a promising inhibitory target.

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来源期刊

Nature Reviews Immunology 医学-免疫学

CiteScore

93.40

自引率

0.40%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.