Cell intrinsic role of NF-κB-inducing kinase in regulating T cell-mediated immune and autoimmune responses
Year: 2016
Type: article
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.
Source: Scientific Reports
DOI: 10.1038/srep22115
Institutions: The University of Texas MD Anderson Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, Tsinghua University, Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy, Genentech
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G1012634304, G2007522317, Regulation of T-cell function and autoimmune inflammation by deubiquitinases., G293715275, G3003483119, Regulation of T-cell function and autoimmune inflammation by deubiquitinase CYLD, Molecular Studies of Noncanonical NF-kb Signaling, G9000040331, Cancer Center Support Grant
OpenAlex ID: W2404315308