CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD

Guangxi Zhou, Lin Yu, Leilei Fang, Wenjing Yang, Tianming Yu, Yinglei Miao, Minhu Chen, Kaichun Wu, Feidi Chen, Yingzi Cong, Zhanju Liu

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1052-1063
Number of pages12
JournalGut
Volume67
Issue number6
DOIs
StatePublished - Jun 1 2018

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Keywords

  • CELLULAR IMMUNOLOGY
  • IBD BASIC RESEARCH
  • INTERLEUKINS
  • MUCOSAL IMMUNOLOGY

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Zhou, G., Yu, L., Fang, L., Yang, W., Yu, T., Miao, Y., Chen, M., Wu, K., Chen, F., Cong, Y., & Liu, Z. (2018). CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. Gut, 67(6), 1052-1063. https://doi.org/10.1136/gutjnl-2016-313535