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TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling

Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a...

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Autores principales: Jin, Jin, Xiao, Yichuan, Chang, Jae-Hoon, Yu, Jiayi, Hu, Hongbo, Starr, Robyn, Brittain, George C., Chang, Mikyoung, Cheng, Xuhong, Sun, Shao-Cong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477307/
https://www.ncbi.nlm.nih.gov/pubmed/23023393
http://dx.doi.org/10.1038/ni.2423
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author Jin, Jin
Xiao, Yichuan
Chang, Jae-Hoon
Yu, Jiayi
Hu, Hongbo
Starr, Robyn
Brittain, George C.
Chang, Mikyoung
Cheng, Xuhong
Sun, Shao-Cong
author_facet Jin, Jin
Xiao, Yichuan
Chang, Jae-Hoon
Yu, Jiayi
Hu, Hongbo
Starr, Robyn
Brittain, George C.
Chang, Mikyoung
Cheng, Xuhong
Sun, Shao-Cong
author_sort Jin, Jin
collection PubMed
description Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a pivotal negative regulator of IgA class switching. B cell-specific TBK1 ablation in mice resulted in uncontrolled production of IgA and development of nephropathy-like disease symptoms. TBK1 negatively regulated IgA class switching by attenuating noncanonical NF-κB signaling, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase. These findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and highlight a unique mechanism that controls IgA production.
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spelling pubmed-34773072013-05-01 TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling Jin, Jin Xiao, Yichuan Chang, Jae-Hoon Yu, Jiayi Hu, Hongbo Starr, Robyn Brittain, George C. Chang, Mikyoung Cheng, Xuhong Sun, Shao-Cong Nat Immunol Article Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a pivotal negative regulator of IgA class switching. B cell-specific TBK1 ablation in mice resulted in uncontrolled production of IgA and development of nephropathy-like disease symptoms. TBK1 negatively regulated IgA class switching by attenuating noncanonical NF-κB signaling, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase. These findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and highlight a unique mechanism that controls IgA production. 2012-09-30 2012-11 /pmc/articles/PMC3477307/ /pubmed/23023393 http://dx.doi.org/10.1038/ni.2423 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jin, Jin
Xiao, Yichuan
Chang, Jae-Hoon
Yu, Jiayi
Hu, Hongbo
Starr, Robyn
Brittain, George C.
Chang, Mikyoung
Cheng, Xuhong
Sun, Shao-Cong
TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title_full TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title_fullStr TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title_full_unstemmed TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title_short TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
title_sort tbk1 controls iga class switching by negatively regulating noncanonical nf-κb signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477307/
https://www.ncbi.nlm.nih.gov/pubmed/23023393
http://dx.doi.org/10.1038/ni.2423
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