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CD177 + neutrophils as functionally activated neutrophils negatively regulate IBD
Gut ( IF 24.5 ) Pub Date : 2017-05-03 , DOI: 10.1136/gutjnl-2016-313535
Guangxi Zhou , Lin Yu , Leilei Fang , Wenjing Yang , Tianming Yu , Yinglei Miao , Minhu Chen , Kaichun Wu , Feidi Chen , Yingzi Cong , Zhanju Liu

Background Neutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177+ neutrophils in pathogenesis of IBD remains elusive. Materials and methods Expression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry. CD177+ and CD177− neutrophils were isolated to determine gene differences by RNA sequencing. Colitis was established in CD177−/− and wild-type mice in response to dextran sulfate sodium (DSS) insults to determine the role of CD177+ neutrophils in IBD. Results CD177+ neutrophils were markedly increased in peripheral blood and inflamed mucosa from patients with active IBD compared with healthy controls. RNA sequencing revealed that differential gene expression between CD177+ and CD177− neutrophils from patients with IBD was associated with response to bacterial defence, hydrogen peroxide and reactive oxygen species (ROS). CD177+ neutrophils produced lower levels of proinflammatory cytokines (ie, interferon-γ, interleukin (IL)-6, IL-17A), but higher levels of IL-22 and transforming growth factor-β, and exhibited increased bactericidal activities (ie, ROS, antimicrobial peptides, neutrophil extracellular trap) compared with CD177− subset. CD177−/− mice developed more severe colitis on DSS insults compared with wild-type mice. Moreover, CD177 deficiency led to compromised intestinal barrier and impaired antibacterial immunity through decreased production of IL-22 by CD177− neutrophils. Conclusions CD177+ neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production. Targeting CD177+ neutrophils may be beneficial for treatment of IBD.

中文翻译:

CD177 + 中性粒细胞作为功能激活的中性粒细胞负调节 IBD

背景 中性粒细胞在 IBD 发炎的粘膜中积累,并在发病机制中起重要作用。CD177 在中性粒细胞中特异性表达并在炎症期间上调。然而,CD177+ 中性粒细胞在 IBD 发病机制中的作用仍然难以捉摸。材料和方法 使用定量 RT-PCR、流式细胞术和免疫组织化学分析 IBD 患者外周血和肠粘膜中 CD177 的表达。分离 CD177+ 和 CD177- 中性粒细胞以通过 RNA 测序确定基因差异。结肠炎在 CD177-/- 和野生型小鼠中建立,以响应葡聚糖硫酸钠 (DSS) 的损伤,以确定 CD177+ 中性粒细胞在 IBD 中的作用。结果 与健康对照组相比,活动性 IBD 患者外周血和炎症黏膜中 CD177+ 中性粒细胞显着增加。RNA 测序显示,来自 IBD 患者的 CD177+ 和 CD177- 中性粒细胞之间的差异基因表达与对细菌防御、过氧化氢和活性氧 (ROS) 的反应有关。CD177+ 中性粒细胞产生较低水平的促炎细胞因子(即干扰素-γ、白细胞介素 (IL)-6、IL-17A),但产生较高水平的 IL-22 和转化生长因子-β,并表现出增加的杀菌活性(即 ROS 、抗菌肽、中性粒细胞胞外陷阱)与 CD177- 子集相比。与野生型小鼠相比,CD177-/- 小鼠因 DSS 损伤而发生更严重的结肠炎。而且,CD177 缺乏导致肠道屏障受损,并通过 CD177- 中性粒细胞产生的 IL-22 减少而导致抗菌免疫受损。结论 CD177+ 中性粒细胞代表功能激活的群体,并通过增加杀菌活性和 IL-22 产生在 IBD 中发挥保护作用。靶向 CD177+ 中性粒细胞可能有益于 IBD 的治疗。
更新日期:2017-05-03
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