The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling.
Nat Immunol
; 13(11): 1101-9, 2012 Nov.
Article
en 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
Banco de datos:
MEDLINE
Asunto principal:
Inmunoglobulina A
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FN-kappa B
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Proteínas Serina-Treonina Quinasas
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Cambio de Clase de Inmunoglobulina
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Glomerulonefritis por IGA
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article