IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation.

IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation.
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IL-22调节农业粉尘诱导的气道炎症的炎症反应

DOI:
10.1016/j.taap.2022.116044
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发表时间:
2022-07-01
影响因子:
3.8
通讯作者:
Nordgren TM
Nordgren TM
中科院分区:
医学3区
文献类型:
--
作者:
Ulu A;Sveiven S;Bilg A;Velazquez JV;Diaz M;Mukherjee M;Yuil-Valdes AG;Kota S;Burr A;Najera A;Nordgren TM

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IL-22 是一种独特的细胞因子,在许多慢性炎症性疾病(包括哮喘)中表达上调,并在炎症过程中调节组织反应。然而,IL-22 在炎症消退中的作用以及它如何促进肺部修复过程在很大程度上尚不清楚。在这里,我们测试了这样的假设:IL-22 信号传导对于重复暴露于农业灰尘后的炎症消退至关重要。使用已建立的有机粉尘提取物诱导肺部炎症的小鼠模型,我们发现 IL-22 敲除小鼠对农业粉尘的反应增强,与野生型对照相比,浸润性免疫细胞和肺部病理学加剧增加证明了这一点。我们进一步发现,为了响应灰尘,IL-22 在气道上皮和实质内发现的 Ym1+ 巨噬细胞中表达,以响应灰尘。 IL-22表达的增加伴随着肺上皮内IL-22受体IL-22R1的增加。此外,我们发现体内肺泡巨噬细胞以及体外THP-1细胞表达IL-22,并且这种表达受到粉尘暴露的调节。此外,IL-22 的亚细胞定位似乎位于静息 THP1 人单核细胞的高尔基体中,并且灰尘提取物处理与灰尘提取物暴露期间 IL-22 从高尔基体储存库释放到细胞质区室相关。综上所述,我们发现巨噬细胞介导的 IL-22 信号在灰尘引起的小鼠肺部炎症中发挥着重要作用。
IL-22 is a unique cytokine that is upregulated in many chronic inflammatory diseases, including asthma, and modulates tissue responses during inflammation. However, the role of IL-22 in the resolution of inflammation and how this contributes to lung repair processes are largely unknown. Here, we tested the hypothesis that IL-22 signaling is critical in inflammation resolution after repetitive exposure to agricultural dust. Using an established mouse model of organic dust extract-induced lung inflammation, we found that IL-22 knockout mice have an enhanced response to agricultural dust as evidenced by an exacerbated increase in infiltrating immune cells and lung pathology as compared to wild-type controls. We further identified that, in response to dust, IL-22 is expressed in airway epithelium and in Ym1+ macrophages found within the parenchyma in response to dust. The increase in IL-22 expression was accompanied by increases in IL-22 receptor IL-22R1 within the lung epithelium. In addition, we found that alveolar macrophages in vivo as well as THP-1 cells in vitro express IL-22, and this expression is modulated by dust exposure. Furthermore, subcellular localization of IL-22 appears to be in the Golgi of resting THP1 human monocytes, and treatment with dust extracts is associated with IL-22 release into the cytosolic compartment from the Golgi reservoirs during dust extract exposure. Taken together, we have identified a significant role for macrophage-mediated IL-22 signaling that is activated in dust-induced lung inflammation in mice.
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发表时间: 2020-01-01
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