NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis

Zuliang Jie, Jin Young Yang, Meidi Gu, Hui Wang, Xiaoping Xie, Yanchuan Li, Ting Liu, Lele Zhu, Jianhong Shi, Lingyun Zhang, Xiaofei Zhou, Donghyun Joo, Hans D. Brightbill, Yingzi Cong, Daniel Lin, Xuhong Cheng, Shao Cong Sun

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Dendritic cells (DCs) play an integral role in regulating mucosal immunity and homeostasis, but the signaling network mediating this function of DCs is poorly defined. We identified the noncanonical NF-κB-inducing kinase (NIK) as a crucial mediator of mucosal DC function. DC-specific NIK deletion impaired intestinal immunoglobulin A (IgA) secretion and microbiota homeostasis, rendering mice sensitive to an intestinal pathogen, Citrobacter rodentium. DC-specific NIK was required for expression of the IgA transporter polymeric immunoglobulin receptor (pIgR) in intestinal epithelial cells, which in turn relied on the cytokine IL-17 produced by TH17 cells and innate lymphoid cells (ILCs). NIK-activated noncanonical NF-κB induced expression of IL-23 in DCs, contributing to the maintenance of TH17 cells and type 3 ILCs. Consistent with the dual functions of IL-23 and IL-17 in mucosal immunity and inflammation, NIK deficiency also ameliorated colitis induction. Thus, our data suggest a pivotal role for the NIK signaling axis in regulating DC functions in intestinal immunity and homeostasis.

    Original languageEnglish (US)
    JournalNature Immunology
    DOIs
    StateAccepted/In press - Jan 1 2018

    Fingerprint

    Dendritic Cells
    Immunity
    Homeostasis
    Phosphotransferases
    Interleukin-23
    Th17 Cells
    Mucosal Immunity
    Interleukin-17
    Immunoglobulin A
    Citrobacter rodentium
    Polymeric Immunoglobulin Receptors
    Lymphocytes
    Microbiota
    Colitis
    Epithelial Cells
    Maintenance
    Cytokines
    Inflammation

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. / Jie, Zuliang; Yang, Jin Young; Gu, Meidi; Wang, Hui; Xie, Xiaoping; Li, Yanchuan; Liu, Ting; Zhu, Lele; Shi, Jianhong; Zhang, Lingyun; Zhou, Xiaofei; Joo, Donghyun; Brightbill, Hans D.; Cong, Yingzi; Lin, Daniel; Cheng, Xuhong; Sun, Shao Cong.

    In: Nature Immunology, 01.01.2018.

    Research output: Contribution to journalArticle

    Jie, Z, Yang, JY, Gu, M, Wang, H, Xie, X, Li, Y, Liu, T, Zhu, L, Shi, J, Zhang, L, Zhou, X, Joo, D, Brightbill, HD, Cong, Y, Lin, D, Cheng, X & Sun, SC 2018, 'NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis', Nature Immunology. https://doi.org/10.1038/s41590-018-0206-z
    Jie, Zuliang ; Yang, Jin Young ; Gu, Meidi ; Wang, Hui ; Xie, Xiaoping ; Li, Yanchuan ; Liu, Ting ; Zhu, Lele ; Shi, Jianhong ; Zhang, Lingyun ; Zhou, Xiaofei ; Joo, Donghyun ; Brightbill, Hans D. ; Cong, Yingzi ; Lin, Daniel ; Cheng, Xuhong ; Sun, Shao Cong. / NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. In: Nature Immunology. 2018.
    @article{d11c609944ca4be5b3e329c98ade6c03,
    title = "NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis",
    abstract = "Dendritic cells (DCs) play an integral role in regulating mucosal immunity and homeostasis, but the signaling network mediating this function of DCs is poorly defined. We identified the noncanonical NF-κB-inducing kinase (NIK) as a crucial mediator of mucosal DC function. DC-specific NIK deletion impaired intestinal immunoglobulin A (IgA) secretion and microbiota homeostasis, rendering mice sensitive to an intestinal pathogen, Citrobacter rodentium. DC-specific NIK was required for expression of the IgA transporter polymeric immunoglobulin receptor (pIgR) in intestinal epithelial cells, which in turn relied on the cytokine IL-17 produced by TH17 cells and innate lymphoid cells (ILCs). NIK-activated noncanonical NF-κB induced expression of IL-23 in DCs, contributing to the maintenance of TH17 cells and type 3 ILCs. Consistent with the dual functions of IL-23 and IL-17 in mucosal immunity and inflammation, NIK deficiency also ameliorated colitis induction. Thus, our data suggest a pivotal role for the NIK signaling axis in regulating DC functions in intestinal immunity and homeostasis.",
    author = "Zuliang Jie and Yang, {Jin Young} and Meidi Gu and Hui Wang and Xiaoping Xie and Yanchuan Li and Ting Liu and Lele Zhu and Jianhong Shi and Lingyun Zhang and Xiaofei Zhou and Donghyun Joo and Brightbill, {Hans D.} and Yingzi Cong and Daniel Lin and Xuhong Cheng and Sun, {Shao Cong}",
    year = "2018",
    month = "1",
    day = "1",
    doi = "10.1038/s41590-018-0206-z",
    language = "English (US)",
    journal = "Nature Immunology",
    issn = "1529-2908",
    publisher = "Nature Publishing Group",

    }

    TY - JOUR

    T1 - NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis

    AU - Jie, Zuliang

    AU - Yang, Jin Young

    AU - Gu, Meidi

    AU - Wang, Hui

    AU - Xie, Xiaoping

    AU - Li, Yanchuan

    AU - Liu, Ting

    AU - Zhu, Lele

    AU - Shi, Jianhong

    AU - Zhang, Lingyun

    AU - Zhou, Xiaofei

    AU - Joo, Donghyun

    AU - Brightbill, Hans D.

    AU - Cong, Yingzi

    AU - Lin, Daniel

    AU - Cheng, Xuhong

    AU - Sun, Shao Cong

    PY - 2018/1/1

    Y1 - 2018/1/1

    N2 - Dendritic cells (DCs) play an integral role in regulating mucosal immunity and homeostasis, but the signaling network mediating this function of DCs is poorly defined. We identified the noncanonical NF-κB-inducing kinase (NIK) as a crucial mediator of mucosal DC function. DC-specific NIK deletion impaired intestinal immunoglobulin A (IgA) secretion and microbiota homeostasis, rendering mice sensitive to an intestinal pathogen, Citrobacter rodentium. DC-specific NIK was required for expression of the IgA transporter polymeric immunoglobulin receptor (pIgR) in intestinal epithelial cells, which in turn relied on the cytokine IL-17 produced by TH17 cells and innate lymphoid cells (ILCs). NIK-activated noncanonical NF-κB induced expression of IL-23 in DCs, contributing to the maintenance of TH17 cells and type 3 ILCs. Consistent with the dual functions of IL-23 and IL-17 in mucosal immunity and inflammation, NIK deficiency also ameliorated colitis induction. Thus, our data suggest a pivotal role for the NIK signaling axis in regulating DC functions in intestinal immunity and homeostasis.

    AB - Dendritic cells (DCs) play an integral role in regulating mucosal immunity and homeostasis, but the signaling network mediating this function of DCs is poorly defined. We identified the noncanonical NF-κB-inducing kinase (NIK) as a crucial mediator of mucosal DC function. DC-specific NIK deletion impaired intestinal immunoglobulin A (IgA) secretion and microbiota homeostasis, rendering mice sensitive to an intestinal pathogen, Citrobacter rodentium. DC-specific NIK was required for expression of the IgA transporter polymeric immunoglobulin receptor (pIgR) in intestinal epithelial cells, which in turn relied on the cytokine IL-17 produced by TH17 cells and innate lymphoid cells (ILCs). NIK-activated noncanonical NF-κB induced expression of IL-23 in DCs, contributing to the maintenance of TH17 cells and type 3 ILCs. Consistent with the dual functions of IL-23 and IL-17 in mucosal immunity and inflammation, NIK deficiency also ameliorated colitis induction. Thus, our data suggest a pivotal role for the NIK signaling axis in regulating DC functions in intestinal immunity and homeostasis.

    UR - http://www.scopus.com/inward/record.url?scp=85053790780&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85053790780&partnerID=8YFLogxK

    U2 - 10.1038/s41590-018-0206-z

    DO - 10.1038/s41590-018-0206-z

    M3 - Article

    JO - Nature Immunology

    JF - Nature Immunology

    SN - 1529-2908

    ER -