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

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

Research output: Contribution to journalArticle

108 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

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Inflammasomes
Neutrophil Infiltration
Urticaria
Interleukin-1
Mast Cells
Histamine
Blood Vessels
Cryopyrin-Associated Periodic Syndromes
Skin
Exanthema
Mastocytosis
Caspase 1
Leucine
Neutrophils
Nucleotides
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. / Nakamura, Yuumi; Kambe, Naotomo; Saito, Megumu; Nishikomori, Ryuta; Kim, Yungi; Murakami, Makoto; Núñez, Gabriel; Matsue, Hiroyuki.

In: Journal of Experimental Medicine, Vol. 206, No. 5, 11.05.2009, p. 1037-1046.

Research output: Contribution to journalArticle

Nakamura, Yuumi ; Kambe, Naotomo ; Saito, Megumu ; Nishikomori, Ryuta ; Kim, Yungi ; Murakami, Makoto ; Núñez, Gabriel ; Matsue, Hiroyuki. / Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 5. pp. 1037-1046.
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