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

    26 Citations (Scopus)

    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

    Fingerprint

    Neutrophils
    RNA Sequence Analysis
    Dextran Sulfate
    Colitis
    Reactive Oxygen Species
    Mucous Membrane
    Interleukin-17
    Transforming Growth Factors
    Intestinal Mucosa
    Interferons
    Hydrogen Peroxide
    Immunity
    Interleukin-6
    Flow Cytometry
    Immunohistochemistry
    Cytokines
    Inflammation
    Gene Expression
    Polymerase Chain Reaction
    Peptides

    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., ... 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

    CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. / Zhou, Guangxi; Yu, Lin; Fang, Leilei; Yang, Wenjing; Yu, Tianming; Miao, Yinglei; Chen, Minhu; Wu, Kaichun; Chen, Feidi; Cong, Yingzi; Liu, Zhanju.

    In: Gut, Vol. 67, No. 6, 01.06.2018, p. 1052-1063.

    Research output: Contribution to journalArticle

    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, vol. 67, no. 6, pp. 1052-1063. https://doi.org/10.1136/gutjnl-2016-313535
    Zhou, Guangxi ; Yu, Lin ; Fang, Leilei ; Yang, Wenjing ; Yu, Tianming ; Miao, Yinglei ; Chen, Minhu ; Wu, Kaichun ; Chen, Feidi ; Cong, Yingzi ; Liu, Zhanju. / CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. In: Gut. 2018 ; Vol. 67, No. 6. pp. 1052-1063.
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    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.",
    keywords = "CELLULAR IMMUNOLOGY, IBD BASIC RESEARCH, INTERLEUKINS, MUCOSAL IMMUNOLOGY",
    author = "Guangxi Zhou and Lin Yu and Leilei Fang and Wenjing Yang and Tianming Yu and Yinglei Miao and Minhu Chen and Kaichun Wu and Feidi Chen and Yingzi Cong and Zhanju Liu",
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    T1 - CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD

    AU - Zhou, Guangxi

    AU - Yu, Lin

    AU - Fang, Leilei

    AU - Yang, Wenjing

    AU - Yu, Tianming

    AU - Miao, Yinglei

    AU - Chen, Minhu

    AU - Wu, Kaichun

    AU - Chen, Feidi

    AU - Cong, Yingzi

    AU - Liu, Zhanju

    PY - 2018/6/1

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    N2 - 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.

    AB - 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.

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    KW - IBD BASIC RESEARCH

    KW - INTERLEUKINS

    KW - MUCOSAL IMMUNOLOGY

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