title: Cell intrinsic role of NF-κB-inducing kinase in regulating T cell-mediated immune and autoimmune responses.
abstract: NF-κB inducing kinase (NIK) is a central component of the noncanonical NF-κB signaling pathway. Although NIK has been extensively studied for its function in the regulation of lymphoid organ development and B-cell maturation, the role of NIK in regulating T cell functions remains unclear and controversial. Using T cell-conditional NIK knockout mice, we here demonstrate that although NIK is dispensable for thymocyte development, it has a cell-intrinsic role in regulating the homeostasis and function of peripheral T cells. T cell-specific NIK ablation reduced the frequency of effector/memory-like T cells and impaired T cell responses to bacterial infection. The T cell-conditional NIK knockout mice were also defective in generation of inflammatory T cells and refractory to the induction of a T cell-dependent autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest a crucial role for NIK in mediating the generation of effector T cells and their recall responses to antigens. Together, these findings establish NIK as a cell-intrinsic mediator of T cell functions in both immune and autoimmune responses.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing, China.|Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Yanchuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Lele
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Immunology, Genentech Inc., South San Francisco, CA 94080.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Brightbill
authors.affiliation: Department of Immunology, Genentech Inc., South San Francisco, CA 94080.
authors.forename: Lawren C
authors.initials: LC
authors.lastname: Wu
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA.|The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D001424:Bacterial Infections / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006706:Homeostasis; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D060168:Thymocytes / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase