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A recombinant protein rLZ-8, originally extracted from Ganoderma lucidum, ameliorates OVA-induced lung inflammation by regulating Th17/Treg balance.
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-06-24 , DOI: 10.1002/jlb.5ma0420-453r Huazhen Liu 1, 2 , Feifei Qiu 1 , Yuanyuan Wang 1 , Feng Liang 3 , Jian Liang 2, 4 , Chengchuan Lin 1 , Jiandong Liang 3 , Boliang Gong 3 , Shamyuen Chan 3 , Zhong- De Zhang 1 , Xiaoping Lai 4 , Shaozhen Hou 2, 3 , Zhenhua Dai 1
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-06-24 , DOI: 10.1002/jlb.5ma0420-453r Huazhen Liu 1, 2 , Feifei Qiu 1 , Yuanyuan Wang 1 , Feng Liang 3 , Jian Liang 2, 4 , Chengchuan Lin 1 , Jiandong Liang 3 , Boliang Gong 3 , Shamyuen Chan 3 , Zhong- De Zhang 1 , Xiaoping Lai 4 , Shaozhen Hou 2, 3 , Zhenhua Dai 1
Affiliation
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Asthma is one of the most common chronic and inflammatory respiratory diseases, which is estimated to affect 1–10% of the population in different regions across the world. Previous studies have shown that recombinant Ling‐Zhi 8 (rLZ‐8), an immunoregulatory protein originally extracted from Ganoderma lucidum , plays multiple roles in regulating murine immune cells, including T cells. Here, we examined whether rLZ‐8 would ameliorate pulmonary inflammation in a model of asthma‐like mice. We found that rLZ‐8 significantly inhibited the lung inflammation and reduced infiltration of inflammatory cells, including dendritic cells and eosinophils, in OVA‐induced asthmatic mice. It also deceased IL‐17A level but increased IL‐10 level in bronchoalveolar lavage fluid (BALF) while reducing RORγt mRNA expression and enhancing Foxp3 mRNA level in the lung tissue. Flow cytometry studies demonstrated that rLZ‐8 remarkably down‐regulated Th17 cells but upregulated Foxp3+ regulatory T (Treg) cells, rather than influencing Th1 versus Th2 cells. Experiments in vitro also showed that rLZ‐8 suppressed murine CD3+ T cell proliferation and reduced the frequency of Th17 cells while promoting the differentiation of CD4+Foxp3+ Tregs. Moreover, rIL‐8 similarly altered human Th17/Treg generation or their balance in vitro. Finally, we found that rLZ‐8 suppressed signaling pathways of both STAT3 and NF‐κB (P100/P52) in murine lung tissue as well as cultured T cells. Thus, we have demonstrated that rLZ‐8 attenuates pulmonary inflammation through regulating the balance of Th17/Treg cells in OVA‐induced asthmatic mice and that rLZ‐8 may be a potential therapeutic agent for the treatment of asthma in clinic.
中文翻译：
最初从灵芝提取的重组蛋白rLZ-8可通过调节Th17 / Treg平衡来缓解OVA诱导的肺部炎症。
哮喘是最常见的慢性和炎性呼吸道疾病之一，据估计，它会影响全球不同地区1-10％的人口。先前的研究表明，重组灵芝8（rLZ-8）是一种最初从灵芝中提取的免疫调节蛋白。，在调节鼠类免疫细胞（包括T细胞）中发挥多种作用。在这里，我们检查了rLZ-8是否会改善哮喘样小鼠模型中的肺部炎症。我们发现，在OVA诱发的哮喘小鼠中，rLZ-8可以显着抑制肺部炎症并减少炎症细胞（包括树突状细胞和嗜酸性粒细胞）的浸润。它也降低了IL-17A水平，但增加了支气管肺泡灌洗液（BALF）中的IL-10水平，同时降低了RORγtmRNA表达并增强了肺组织中的Foxp3 mRNA水平。流式细胞仪研究表明，rLZ-8显着下调了Th17细胞，但上调了Foxp3 +调节性T（Treg）细胞，而不影响Th1与Th2细胞。体外实验还表明，rLZ-8抑制了鼠CD3 +T细胞增殖并降低Th17细胞的频率，同时促进CD4 + Foxp3 + Tregs的分化。此外，rIL-8在体外也类似地改变了人类Th17 / Treg的生成或其平衡。最后，我们发现rLZ-8抑制了鼠肺组织以及培养的T细胞中STAT3和NF-κB（P100 / P52）的信号通路。因此，我们证明rLZ-8通过调节OVA诱发的哮喘小鼠中的Th17 / Treg细胞平衡来减轻肺部炎症，并且rLZ-8可能是临床上治疗哮喘的潜在治疗剂。
更新日期：2020-08-04
中文翻译：
最初从灵芝提取的重组蛋白rLZ-8可通过调节Th17 / Treg平衡来缓解OVA诱导的肺部炎症。
哮喘是最常见的慢性和炎性呼吸道疾病之一，据估计，它会影响全球不同地区1-10％的人口。先前的研究表明，重组灵芝8（rLZ-8）是一种最初从灵芝中提取的免疫调节蛋白。，在调节鼠类免疫细胞（包括T细胞）中发挥多种作用。在这里，我们检查了rLZ-8是否会改善哮喘样小鼠模型中的肺部炎症。我们发现，在OVA诱发的哮喘小鼠中，rLZ-8可以显着抑制肺部炎症并减少炎症细胞（包括树突状细胞和嗜酸性粒细胞）的浸润。它也降低了IL-17A水平，但增加了支气管肺泡灌洗液（BALF）中的IL-10水平，同时降低了RORγtmRNA表达并增强了肺组织中的Foxp3 mRNA水平。流式细胞仪研究表明，rLZ-8显着下调了Th17细胞，但上调了Foxp3 +调节性T（Treg）细胞，而不影响Th1与Th2细胞。体外实验还表明，rLZ-8抑制了鼠CD3 +T细胞增殖并降低Th17细胞的频率，同时促进CD4 + Foxp3 + Tregs的分化。此外，rIL-8在体外也类似地改变了人类Th17 / Treg的生成或其平衡。最后，我们发现rLZ-8抑制了鼠肺组织以及培养的T细胞中STAT3和NF-κB（P100 / P52）的信号通路。因此，我们证明rLZ-8通过调节OVA诱发的哮喘小鼠中的Th17 / Treg细胞平衡来减轻肺部炎症，并且rLZ-8可能是临床上治疗哮喘的潜在治疗剂。
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