机构：[1]Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[2]Department of Pathogenic Biology andImmunology, Xuzhou Medical University, Xuzhou, China[3]Department of Laboratory Medicine, West China Second University Hospital, State KeyLaboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China[4]Central Laboratory, Affiliated Hospitalof Hebei University, Baoding, China河北大学附属医院[5]Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospitalof Zhengzhou University, Zhengzhou, China[6]Department of Immunology, Genentech, Inc.,South San Francisco, CA, USA[7]Department of Pathologyand Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA[8]MD Anderson Cancer CenterUT Health Graduate School of Biomedical Sciences, Houston, TX, USA
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-kappa B-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 T(H)17 cells and innate lymphoid cells (ILCs). NIK-activated noncanonical NF-kappa B induced expression of IL-23 in DCs, contributing to the maintenance of T(H)17 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.
基金：
National Institutes of Health [GM84459, AI057555, AI104519, AI64639]; NIH/NCI [P30CA016672]
第一作者机构：[1]Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
共同第一作者：
通讯作者：
通讯机构：[1]Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[8]MD Anderson Cancer CenterUT Health Graduate School of Biomedical Sciences, Houston, TX, USA
推荐引用方式(GB/T 7714)：
Zuliang Jie,Jin-Young Yang,Meidi Gu,et al.NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis[J].NATURE IMMUNOLOGY.2018,19(11):1224-+.doi:10.1038/s41590-018-0206-z.
APA：
Zuliang Jie,Jin-Young Yang,Meidi Gu,Hui Wang,Xiaoping Xie...&Shao-Cong Sun.(2018).NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis.NATURE IMMUNOLOGY,19,(11)
MLA：
Zuliang Jie,et al."NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis".NATURE IMMUNOLOGY 19..11(2018):1224-+
医学