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

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    3 Scopus citations

    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

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Jie, Z., Yang, J. Y., Gu, M., Wang, H., Xie, X., Li, Y., Liu, T., Zhu, L., Shi, J., Zhang, L., Zhou, X., Joo, D., Brightbill, H. D., Cong, Y., Lin, D., Cheng, X., & Sun, S. C. (Accepted/In press). NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. Nature Immunology. https://doi.org/10.1038/s41590-018-0206-z