The Inflammasome, an Innate Immunity Guardian, Participates in Skin Urticarial Reactions and Contact Hypersensitivity
The Inflammasome, an Innate Immunity Guardian, Participates in Skin Urticarial Reactions and Contact Hypersensitivity
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DOI：
10.2332/allergolint.09-rai-0160
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发表时间：
2010-06-01
影响因子：
6.8
通讯作者：
Nishikomori, Ryuta
中科院分区：
文献类型：
--
作者：
Kambe, Naotomo;Nakamura, Yuumi;Nishikomori, Ryuta
荨麻疹是cryopyrin-associated periodic syndrome（CAPS）的特征性临床表现之一，由NLRP 3（核苷酸结合寡聚化结构域，富含亮氨酸重复序列家族，pyrin结构域3）编码基因突变引起。这种细胞内模式识别受体及其衔接蛋白，称为细胞凋亡相关的斑点样蛋白，含有半胱天冬酶募集和激活结构域（ASC），参与形成称为炎性体的多蛋白复合物。炎性小体负责响应微生物和内源性刺激而激活半胱天冬酶-1。通过对CAPS中荨麻疹细胞机制的分析，我们追踪到CAPS中caspase-1激活的IL-1 β有一个令人惊讶的来源：肥大细胞。最近，两个研究小组已经产生了携带NIrp 3突变的基因靶向小鼠。这些小鼠具有非常严重的表型，具有延迟的生长和皮炎的发展，但不是荨麻疹。用CAPS和这些基因敲入小鼠观察到的皮肤表现差异的原因与以下发现有关：炎性小体也在接触性超敏反应中起作用，并且IL-18（另一种参与炎性小体激活半胱天冬酶-1的细胞因子）可能是皮炎发展的主要参与者。
Urticarial rash, one of the clinical manifestations characteristic of cryopyrin-associated periodic syndrome (CAPS), is caused by a mutation in the gene encoding for NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeats containing family, pyrin domain containing 3). This intracellular pattern recognition receptor and its adaptor protein, called apoptosis associated speck-like protein containing a caspase-recruitment and activating domain (ASC), participate in the formation of a multi-protein complex termed the inflammasome. The inflammasome is responsible for activating caspase-1 in response to microbial and endogenous stimuli. From the analysis of cellular mechanisms of urticarial rash in CAPS, we have traced caspase-1 activated IL-1 beta in CAPS to a surprising source: mast cells. Recently, two groups have generated gene-targeted mice that harbored NIrp3 mutations. These mice had very severe phenotypes, with delayed growth and the development of dermatitis, but not urticaria. The reason for the differences in the skin manifestations observed with CAPS and these knock-in mice relates to the findings that the inflammasome also plays a role in contact hypersensitivity, and that IL-18, another cytokine involved with inflammasome-activation of caspase-1, may be a major player in dermatitis development.