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CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD
  1. Guangxi Zhou1,
  2. Lin Yu1,
  3. Leilei Fang1,
  4. Wenjing Yang1,
  5. Tianming Yu1,
  6. Yinglei Miao2,
  7. Minhu Chen3,
  8. Kaichun Wu4,
  9. Feidi Chen5,
  10. Yingzi Cong5,
  11. Zhanju Liu1
  1. 1Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
  2. 2Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
  3. 3Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  4. 4Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
  5. 5Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
  1. Correspondence to Professor Zhanju Liu, Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China; liuzhanju88{at}126.com; Dr Yingzi Cong, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; yicong{at}utmb.edu

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.

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

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Footnotes

  • *GZ and LY co-first authors.

  • Contributors ZL designed and conducted the experiments, acquired and analysed the data; GZ, LY and LF performed all experiments; WY, TY, YM, MC, KW and FC analysed the data; LF and WY contributed to the clinical data and specimens; GZ, YC and ZL wrote the manuscript. All authors discussed and revised the manuscript.

  • Funding This work was financially supported by grants from the National Natural Science Foundation of China (81630017, 81470822).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Institutional Review Board for Clinical Research of the Shanghai Tenth People's Hospital of Tongji University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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