The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling.
Nat Immunol
; 13(11): 1101-9, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23023393
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-κB, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and identify a unique mechanism that controls IgA production.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina A
/
NF-kappa B
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Proteínas Serina-Treonina Quinases
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Switching de Imunoglobulina
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Glomerulonefrite por IGA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article