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

研究成果: Article査読

124 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1037-1046
ページ数10
ジャーナルJournal of Experimental Medicine
206
5
DOI
出版ステータスPublished - 2009 5月 11
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

フィンガープリント

「Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル