NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil activation in pyoderma gangrenosum across human and murine models.

Authors

Takeshi Araki, Akihiko Uchiyama, Rimu Takata, Keiji Kosaka, Mayu Ohtaka, Shintaro Saito, Takayuki Shuto, Akiko Sekiguchi, Sachiko Ogino, Yoko Yokoyama, Ryoko Torii, Yuki Watanuki, Sei-Ichiro Motegi

Published in

JID innovations : skin science from molecules to population health. Volume 6. Issue 5. Pages 100512. Epub Jul 31, 2026.

Abstract

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, nonhealing cutaneous ulcers. Although dysregulated innate immunity and neutrophil activation are implicated in its pathogenesis, the underlying molecular mechanisms remain poorly defined. This study aimed to identify conserved pathogenic mechanisms by integrating analyses of human PG lesions and a brequinar-induced PG-like murine model and to assess therapeutic relevance. Skin biopsy specimens from patients with PG and publicly available RNA-sequencing data were analyzed alongside the murine model using histological and transcriptomic approaches. Cross-species transcriptomic integration identified shared inflammatory pathways between human and murine PG. Human PG lesions showed increased neutrophil infiltration, neutrophil extracellular trap formation, and a dominant type 1 inflammatory profile, all of which were recapitulated in the brequinar-induced mouse model, together with impaired wound healing. Transcriptomic analyses revealed enhanced oxidative stress responses and activation of the NLRP3/caspase-1 inflammasome pathway as a conserved pathogenic axis. In the murine model, both prednisolone and avacopan suppressed inflammatory cytokine expression and neutrophil activation; however, only avacopan significantly improved wound healing. Collectively, these findings suggest that NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil extracellular trap formation and may represent a PG-associated inflammatory pathway.

PMID:
42604100
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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