Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria

Yuumi Nakamura, Naotomo Kambe, Megumu Saito, Ryuta Nishikomori, Yun Gi Kim, Makoto Murakami, Gabriel Núñez, Hiroyuki Matsue

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain-leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti-interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome.

Original languageEnglish
Pages (from-to)1037-1046
Number of pages10
JournalJournal of Experimental Medicine
Volume206
Issue number5
DOIs
Publication statusPublished - 2009 May 11
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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