The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-kappa B signaling

Title
The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-kappa B signaling
Author(s)
장재훈Jin Jin[Jin Jin]Yichuan Xiao[Yichuan Xiao]Hongbo Hu[Hongbo Hu]Robyn Starr[Robyn Starr]George C Brittain[George C Brittain]Mykeong Chang[Mykeong Chang]Xuhong Cheng[Xuhong Cheng]Shao-Cong Sun[Shao-Cong Sun]Jiayi Yu[Jiayi Yu]
Keywords
INNATE IMMUNITY; SPLENIC MICROARCHITECTURE; ANTIVIRAL RESPONSE; VIRAL-INFECTION; LAMINA PROPRIA; DEFICIENT MICE; CROSS-TALK; RECEPTOR; ACTIVATION; CELLS
Issue Date
201211
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE IMMUNOLOGY, v.13, no.11, pp.1101 - 1109
Abstract
Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NF-kappa B, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-kappa B-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-kappa B pathway and identify a unique mechanism that controls IgA production.
URI
http://hdl.handle.net/YU.REPOSITORY/27017http://dx.doi.org/10.1038/ni.2423
ISSN
1529-2908
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약학대학 > 약학부 > Articles
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