Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria.
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria.
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DOI：
10.1084/jem.20082179
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发表时间：
2009-05-11
期刊：
影响因子：
--
通讯作者：
Matsue H
中科院分区：
文献类型：
--
作者：
Nakamura Y;Kambe N;Saito M;Nishikomori R;Kim YG;Murakami M;Núñez G;Matsue H
抗白细胞介素1(IL-1)治疗可有效抑制由核苷酸结合寡聚结构域-富含亮氨酸重复序列(NLRP3)突变引起的低温吡喃相关周期综合征(CAPS)中的麻风皮疹，提示IL-1β在皮肤中的病理生理作用。然而，调节CAPS患者皮肤中IL-1β产生的细胞机制仍不清楚。我们发现肥大细胞(MC)是CAPS患者皮肤产生IL-1β的主要细胞群。与需要用促炎刺激刺激产生IL-1β的正常MC不同，CAPS患者的常驻MC结构性地产生IL-1β。原代MC在微生物刺激下表达炎症体成分，并通过NLRP3和含有半胱氨酸天冬氨酸酶募集结构域的凋亡相关斑点样蛋白分泌IL-1β。此外，表达与疾病相关但不表达野生型NLRP3的MC在移植到小鼠皮肤中时，会分泌IL-1β，并诱导中性粒细胞迁移和血管渗漏，这是荨麻疹的组织学特征。我们的发现表明，MC在皮肤中是IL-1β的生产者，并通过NLRP3炎症体成为组胺非依赖性荨麻疹的介体。
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.
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影响因子：
4.4
作者：
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通讯作者：
Re, Fabio
DOI：
10.1073/pnas.0611496104
发表时间：
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影响因子：
11.1
作者：
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影响因子：
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作者：
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