在真菌感染过程中，自分泌的白细胞介素-17A（IL-17A）-白细胞介素-17RC（IL-17RC）相互作用激活中性粒细胞，其受白细胞介素-6（IL-6）、白细胞介素-23（IL-23）、视黄酸相关 orphan 受体γt（RORγt）和 dectin-2 调节。

Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2.

机构信息

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.

1] Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA. [2].

出版信息

Nat Immunol. 2014 Feb;15(2):143-51. doi: 10.1038/ni.2797. Epub 2013 Dec 22.

DOI:10.1038/ni.2797

PMID:24362892

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3972892/

Abstract

Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor RORγt and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and RORγt, but not T cells or natural killer (NK) cells, were required for IL-17 production in neutrophils. IL-6 and IL-23 induced expression of the receptors IL-17RC and dectin-2 on neutrophils, and IL-17RC expression was augmented by activation of dectin-2. Autocrine activity of IL-17A and its receptor induced the production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus-induced keratitis. Human neutrophils also expressed RORγt and induced the expression of IL-17A, IL-17RC and dectin-2 following stimulation with IL-6 and IL-23. Our findings identify a population of human and mouse neutrophils with autocrine IL-17 activity that probably contribute to the etiology of microbial and inflammatory diseases.

摘要

在这里，我们鉴定出一群骨髓中性粒细胞，它们组成性地表达转录因子 RORγt，并产生和响应白细胞介素 17A (IL-17A (IL-17))。IL-6、IL-23 和 RORγt，但不是 T 细胞或自然杀伤 (NK) 细胞，是中性粒细胞中 IL-17 产生所必需的。IL-6 和 IL-23 诱导中性粒细胞表达白细胞介素 17RC 和 dectin-2 受体，而 dectin-2 的激活增强了 IL-17RC 的表达。IL-17A 和其受体的自分泌活性诱导活性氧 (ROS) 的产生，并增加体外和曲霉诱导的角膜炎模型中的真菌杀伤作用。人类中性粒细胞也表达 RORγt，并在受到 IL-6 和 IL-23 刺激后诱导 IL-17A、IL-17RC 和 dectin-2 的表达。我们的研究结果确定了一群具有自分泌 IL-17 活性的人类和小鼠中性粒细胞，它们可能有助于微生物和炎症性疾病的病因。