当前位置: X-MOL 学术J. Allergy Clin. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.jaci.2020.08.024
Emily Howard 1 , Gavin Lewis 2 , Lauriane Galle-Treger 1 , Benjamin P Hurrell 1 , Doumet Georges Helou 1 , Pedram Shafiei-Jahani 1 , Jacob D Painter 1 , German Aleman Muench 2 , Pejman Soroosh 2 , Omid Akbari 1
Affiliation  

Background

Group 2 innate lymphoid cells (ILC2s) are the dominant innate lymphoid cell population in the lungs at steady state, and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity. Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210s).

Objective

Our aim was to characterize the effector functions of ILC210s in the development and pathology of allergic asthma.

Methods

IL-4–stimulated ILC210s were isolated to evaluate cytokine secretion, transcription factor signaling, metabolic dependence, and effector functions in vitro. ILC210s were also adoptively transferred into Rag2–/–γc–/– mice, which were then challenged with IL-33 and assessed for airway hyperreactivity and lung inflammation.

Results

We have determined that the transcription factors cMaf and Blimp-1 regulate IL-10 expression in ILC210s. Strikingly, our results demonstrate that ILC210s can utilize both autocrine and paracrine signaling to suppress proinflammatory ILC2 effector functions in vitro. Further, this subset dampens airway hyperreactivity and significantly reduces lung inflammation in vivo. Interestingly, ILC210s demonstrated a metabolic dependency on the glycolytic pathway for IL-10 production, shifting from the fatty acid oxidation pathway conventionally utilized for proinflammatory effector functions.

Conclusion

These findings provide an important and previously unrecognized role of ILC210s in diseases associated with ILC2s such as allergic lung inflammation and asthma. They also provide new insights into the metabolism dependency of proinflammatory and anti-inflammatory ILC2 phenotypes.



中文翻译:


ILC2 产生 IL-10 需要 Blimp-1 和 cMaf,调节细胞代谢并改善气道高反应性


 背景


第 2 组先天淋巴细胞 (ILC2) 是稳态时肺部的主要先天淋巴细胞群,它们释放的 2 型细胞因子是响应嗜酸性粒细胞浸润和气道高反应性增加的主要驱动因素。我们的实验室在肺部发现了一个独特的 ILC2 子集,可以主动产生 IL-10 (ILC2 10 s)。

 客观的


我们的目的是表征 ILC2 10在过敏性哮喘的发展和病理学中的效应器功能。

 方法


分离 IL-4 刺激的 ILC2 10来评估体外细胞因子分泌、转录因子信号传导、代谢依赖性和效应器功能。 ILC2 10也被过继转移到 Rag2 –/– γc –/–小鼠中,然后用 IL-33 攻击并评估气道高反应性和肺部炎症。

 结果


我们已经确定转录因子 cMaf 和 Blimp-1 在 ILC2 10 s 中调节 IL-10 的表达。引人注目的是,我们的结果表明 ILC2 10可以利用自分泌和旁分泌信号在体外抑制促炎 ILC2 效应器功能。此外,该子集可抑制气道高反应性并显着减少体内肺部炎症。有趣的是,ILC2 10表现出对 IL-10 产生的糖酵解途径的代谢依赖性,从传统上用于促炎效应功能的脂肪酸氧化途径转变。

 结论


这些发现提供了 ILC2 10在与 ILC2 相关的疾病(例如过敏性肺部炎症和哮喘)中的重要且先前未被认识的作用。它们还为促炎和抗炎 ILC2 表型的代谢依赖性提供了新的见解。

更新日期:2020-09-06
down
wechat
bug