The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
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DOI：
10.1371/journal.pone.0179797
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Jones MR
中科院分区：
文献类型：
--
作者：
Kozlowski E;Wasserman GA;Morgan M;O'Carroll D;Ramirez NP;Gummuluru S;Rah JY;Gower AC;Ieong M;Quinton LJ;Mizgerd JP;Jones MR
肺泡巨噬细胞协调肺先天免疫，并且对于早期免疫监视和清除气道中的微生物是必不可少的。炎症信号传导必须足够强大以促进宿主防御，但又足够有限以防止过度的组织损伤。肺中的巨噬细胞利用炎症基因表达的多种转录和转录后机制来微妙地平衡免疫介质的加工。体外研究表明，RNA末端尿苷基转移酶（TUT），包括密切同源的家族成员Zcchc 6（TUT 7）和Zcchc 11（TUT 4），与炎症的转录后调节有关。在体内，我们观察到Zcchc 6在小鼠和人原代巨噬细胞中表达。Zcchc 6缺陷小鼠是可行的，出生在孟德尔比率，并没有表现出可观察到的自发表型在基础条件下。在与S.在肺炎中，Zcchc 6缺陷导致包括IL-6、CXCL 1和CXCL 5的选择细胞因子的表达适度但显著增加。这些发现在体外被概括，其中Zcchc 6缺陷型巨噬细胞表现出类似的细胞因子表达增加，由于细菌刺激。虽然Zcchc 6的丢失也导致肺炎期间嗜中性粒细胞迁移到气道的增加，但这些反应不足以影响宿主对感染的防御。
Alveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro. In vivo, we observed that Zcchc6 is expressed in mouse and human primary macrophages. Zcchc6-deficient mice are viable and born in Mendelian ratios and do not exhibit an observable spontaneous phenotype under basal conditions. Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation. Although loss of Zcchc6 also led to increased neutrophil emigration to the airways during pneumonia, these responses were not sufficient to impact host defense against infection.