Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response
Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response
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DOI：
10.1369/jhc.6a7101.2006
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发表时间：
2007-05-01
影响因子：
3.2
通讯作者：
Tschopp, Juerg
中科院分区：
文献类型：
--
作者：
Kummer, J. Alain;Broekhuizen, Roel;Tschopp, Juerg
几种自身炎症性疾病如Muckle-Wells综合征的特征在于NALP 3/cryopyrin基因的突变。NALP 3和NALP 1蛋白可以组装成炎性体，其激活半胱天冬酶-1，导致促炎细胞因子IL-1 β和IL-18的加工。本研究旨在确定哪些细胞和组织表达NALP 1和NALP 3。开发了单克隆抗体，其使用揭示了NALP 1和NALP 3的不同分布特征。粒细胞、单核细胞（非常弱）、树突细胞以及B和T细胞均表达NALP 1和NALP 3。最高水平的NALP 1存在于T细胞和朗格汉斯细胞中。此外，NALP 1存在于腺上皮结构如胃、肠、肺中，并且令人惊讶地存在于神经元和睾丸中。与NALP 1相反，NALP 3显示出更有限的组织分布，主要在口咽、食管和外宫颈的非角化上皮中表达。此外，在膀胱的尿路上皮层中发现NALP 3表达。同样地，观察到NALP 1和NALP 3之间的亚细胞分布的差异，因为NALP 1主要位于细胞核中，而NALP 3主要位于细胞质中。我们提出，NALP 3在口腔和生殖道上皮细胞中的存在允许快速感知入侵的病原体，从而引发先天免疫反应。
Several autoinflammatory disorders such as Muckle-Wells syndrome are characterized by mutations in the NALP3/cryopyrin gene. NALP3 and NALP1 proteins can assemble to inflammasomes that activate caspase-1, resulting in the processing of proinflammatory cytokines IL-1 beta and IL-18. The present study was designed to determine which cells and tissues express NALP1 and NALP3. Monoclonal antibodies were developed and their use revealed distinct distribution profiles of NALP1 and NALP3. Granulocytes, monocytes (very weakly), dendritic cells, and B and T cells all express NALP1 and NALP3. Highest levels of NALP1 are found in T cells and Langerhans cells. Furthermore, NALP1 is present in glandular epithelial structures such as stomach, gut, lung, and, surprisingly, in neurons and testis. In contrast to NALP1, NALP3 shows a more restricted tissue distribution with expression mainly in non-keratinizing epithelia in the oropharynx, esophagus, and ectocervix. Moreover, NALP3 expression is found in the urothelial layer in the bladder. Likewise, a difference in subcellular distribution between NALP1 and NALP3 is observed because NALP1 is localized mainly in the nucleus, whereas NALP3 is predominantly cytoplasmic. We propose that the presence of NALP3 in epithelial cells lining the oral and genital tracts allows the rapid sensing of invading pathogens, thereby triggering an innate immune response.