IL-17A(+)GM-CSF(+) Neutrophils Are the Major Infiltrating Cells in Interstitial Lung Disease in an Autoimmune Arthritis Model.
IL-17A(+)GM-CSF(+) Neutrophils Are the Major Infiltrating Cells in Interstitial Lung Disease in an Autoimmune Arthritis Model.
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DOI：
10.3389/fimmu.2018.01544
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kim YG
中科院分区：
文献类型：
--
作者：
Kwon OC;Lee EJ;Chang EJ;Youn J;Ghang B;Hong S;Lee CK;Yoo B;Kim YG
为了更好地了解自身免疫性关节炎相关间质性肺病（ILD）的发病机制，我们试图确定患有ILD的SKG小鼠肺浸润细胞的特征。我们在8周龄的SKG小鼠中注射curdlan，并在注射后20周通过PET-MRI和注射后22周的组织学分析确定ILD的存在。流式细胞术检测肺浸润细胞。在注射后14周和22周用Luminex多重细胞因子法分析血清细胞因子，比较ILD发生前后的细胞因子谱。肺组织进行蛋白石多路免疫荧光染色。注射后20周，经curdlan处理的SKG小鼠不仅出现关节炎，还出现肺部炎症并纤维化，这是通过PET-MRI和组织学分析确定的。curdran处理的SKG小鼠肺中积累的炎症细胞大部分是CD11b+Gr1+中性粒细胞，它们共同表达IL-17A和GM-CSF，而不是TNF-α。与注射后14周相比，注射后22周血清GM-CSF、MCP1、IL-17A、IL-23、TSLP和可溶性IL-7Rα水平升高，而IFN-γ、IL-22、IL-6和TNF-α水平不变。此外，在免疫荧光染色的肺组织中观察到IL-23、CXCL5、IL-17A和GM-CSF，但未观察到TNF-α。我们发现IL-17A+GM-CSF+中性粒细胞代表了curdlan处理的SKG小鼠肺部的主要炎症细胞。此外，GM-CSF和IL-17A在ILD的发展中似乎比TNF-α发挥更重要的作用。
To gain a better understanding of the pathogenesis of autoimmune arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD. We injected curdlan in SKG mice at 8 weeks of age, and identified the presence of ILD by PET-MRI at 20 weeks post-injection and histological analysis at 22 weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22 weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed. At 20 weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b+Gr1+ neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-α. Compared with 14 weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and soluble IL-7Rα had increased at 22 weeks post-injection, whereas those of IFN-γ, IL-22, IL-6, and TNF-α remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-α, were observed in immunofluorescent-stained lung tissue. We found that IL-17A+GM-CSF+ neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-α in ILD development.
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影响因子：
4.9
作者：
Castelino FV;Varga J
通讯作者：
Varga J
DOI：
10.4168/aair.2011.3.3.186
发表时间：
2011-07
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Kimura S;Pawankar R;Mori S;Nonaka M;Masuno S;Yagi T;Okubo K
通讯作者：
Okubo K
影响因子：
9.3
作者：
Parajuli B;Sonobe Y;Kawanokuchi J;Doi Y;Noda M;Takeuchi H;Mizuno T;Suzumura A
通讯作者：
Suzumura A
影响因子：
64.8
作者：
NEGISHI, I;MOTOYAMA, N;LOH, DY
通讯作者：
LOH, DY
影响因子：
64.8
作者：
Sakaguchi, N;Takahashi, T;Sakaguchi, S
通讯作者：
Sakaguchi, S