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DAI (DLM-1/ZBP1) es un sensor de ADN citosólico y un activador de la respuesta inmune innata
Akinori Takaoka1, Zhichao Wang, Myoung Kwon Choi
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|July 10, 2007
Resumen
Los investigadores identificaron el DAI (activador dependiente del ADN de los factores reguladores del IFN) como un sensor de ADN citosólico clave. Esta proteína mejora la producción de interferón tipo I, crucial para la inmunidad innata contra los patógenos y en los trastornos autoinmunes.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La inmunidad innata se basa en la detección de patrones moleculares asociados a patógenos (PAMP) a través de receptores celulares.
- El ADN citosólico es un potente activador inmune, con receptores de tipo Toll 9 (TLR9) y sensores no identificados implicados.
- La proteína DLM-1 (ZBP1) fue un sensor candidato con función desconocida.
Objetivo del estudio:
- Identificar y caracterizar un sensor de ADN citosólico involucrado en las respuestas inmunológicas innatas.
- Para aclarar el papel de DLM-1 / ZBP1 en la activación mediada por ADN del interferón de tipo I (IFN).
- Proponer un nuevo nombre, DAI (activador dependiente de ADN de los factores reguladores de IFN), que refleje su función.
Principales métodos:
- La expresión artificial de DAI (DLM-1/ZBP1) en los fibroblastos del ratón.
- La interferencia del ARN (RNAi) para inhibir la expresión del ARNm DAI (DLM-1/ZBP1).
- Estimulación con varias fuentes de ADN y medición de IFN tipo I y inducción de genes inmunes innatos.
- Pruebas para evaluar el DAI (DLM-1/ZBP1) que se une al ADN de doble cadena (dsDNA) y su interacción con IRF3 y TBK1.
Principales resultados:
- La sobreexpresión de DAI (DLM-1/ZBP1) mejoró selectivamente el IFN de tipo I inducido por el ADN y la expresión del gen inmune innato.
- El knockdown mediado por ARN de DAI (DLM-1/ZBP1) inhibió la inducción de genes inmunes mediada por ADN.
- DAI (DLM-1/ZBP1) se une directamente al dsDNA, promoviendo su asociación con IRF3 y TBK1.
Conclusiones:
- DAI (DLM-1/ZBP1) funciona como un sensor de ADN citosólico crítico, activando las respuestas inmunes innatas.
- DAI juega un papel integral en la vía de señalización para la producción de IFN de tipo I mediada por ADN.
- Comprender la función del DAI ofrece información sobre la inmunidad antimicrobiana y los mecanismos de las enfermedades autoinmunes.
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