PMID- 30250187 OWN - NLM STAT- MEDLINE DCOM- 20190422 LR - 20231213 IS - 1529-2916 (Electronic) IS - 1529-2908 (Print) IS - 1529-2908 (Linking) VI - 19 IP - 11 DP - 2018 Nov TI - NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. PG - 1224-1235 LID - 10.1038/s41590-018-0206-z [doi] 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-kappaB-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-kappaB 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. FAU - Jie, Zuliang AU - Jie Z AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Yang, Jin-Young AU - Yang JY AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Gu, Meidi AU - Gu M AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Wang, Hui AU - Wang H AUID- ORCID: 0000-0002-8706-2217 AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China. FAU - Xie, Xiaoping AU - Xie X AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Li, Yanchuan AU - Li Y AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Liu, Ting AU - Liu T AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of Laboratory Medicine, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China. FAU - Zhu, Lele AU - Zhu L AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Shi, Jianhong AU - Shi J AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Central Laboratory, Affiliated Hospital of Hebei University, Baoding, China. FAU - Zhang, Lingyun AU - Zhang L AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Zhou, Xiaofei AU - Zhou X AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Joo, Donghyun AU - Joo D AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Brightbill, Hans D AU - Brightbill HD AD - Department of Immunology, Genentech, Inc., South San Francisco, CA, USA. FAU - Cong, Yingzi AU - Cong Y AD - Department of Pathology and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. FAU - Lin, Daniel AU - Lin D AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Cheng, Xuhong AU - Cheng X AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Sun, Shao-Cong AU - Sun SC AUID- ORCID: 0000-0001-7353-9400 AD - Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ssun@mdanderson.org. AD - MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX, USA. ssun@mdanderson.org. LA - eng GR - R01 AI064639/AI/NIAID NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States GR - R01 GM084459/GM/NIGMS NIH HHS/United States GR - R01 AI057555/AI/NIAID NIH HHS/United States GR - R37 AI064639/AI/NIAID NIH HHS/United States GR - R01 AI104519/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180924 PL - United States TA - Nat Immunol JT - Nature immunology JID - 100941354 RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - Colitis/immunology MH - Dendritic Cells/*immunology MH - Homeostasis/*immunology MH - Immunity, Innate MH - Immunity, Mucosal/*immunology MH - Intestinal Mucosa/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Protein Serine-Threonine Kinases/*immunology MH - Signal Transduction/immunology MH - NF-kappaB-Inducing Kinase PMC - PMC6195481 MID - NIHMS1503647 COIS- Competing financial interests H.D.B. is an employee of Genentech, Inc., and the other authors declare no competing financial interests. Genentech, Inc. provided the Map3k14-flox mice. EDAT- 2018/09/27 06:00 MHDA- 2019/04/23 06:00 PMCR- 2019/03/24 CRDT- 2018/09/26 06:00 PHST- 2017/11/07 00:00 [received] PHST- 2018/08/13 00:00 [accepted] PHST- 2018/09/27 06:00 [pubmed] PHST- 2019/04/23 06:00 [medline] PHST- 2018/09/26 06:00 [entrez] PHST- 2019/03/24 00:00 [pmc-release] AID - 10.1038/s41590-018-0206-z [pii] AID - 10.1038/s41590-018-0206-z [doi] PST - ppublish SO - Nat Immunol. 2018 Nov;19(11):1224-1235. doi: 10.1038/s41590-018-0206-z. Epub 2018 Sep 24.