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El factor de transcripción AP-1 Batf controla la diferenciación T(H) 17 de las proteínas
Barbara U Schraml1, Kai Hildner, Wataru Ise
1Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Nature
|July 7, 2009
Resumen
El factor de transcripción BATF es esencial para el desarrollo de las células T auxiliares 17 (T ((H) 17), que son cruciales para la defensa del huésped e implicadas en enfermedades autoinmunes. La pérdida de BATF perjudica la diferenciación T(H) 17 y protege contra la encefalomielitis autoinmune experimental.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- Los factores de transcripción de la proteína activadora 1 (AP-1) regulan la expresión génica a través de la dimerización.
- BATF, un miembro de la familia AP-1, carece de un dominio de activación canónica y anteriormente se pensaba que inhibe la actividad de AP-1.
- Las células T auxiliares 17 (T(H) 17 son críticas para la inmunidad, pero también están involucradas en la patogénesis autoinmune.
Objetivo del estudio:
- Investigar el papel del BATF del factor de transcripción AP-1 en la diferenciación celular de las células T(H) 17.
- Aclarar los mecanismos moleculares por los cuales el BATF influye en el desarrollo y la función de las células T(H) 17.
Principales métodos:
- Análisis de la diferenciación celular T(H) 17 en ratones con deficiencia de Batf.
- Evaluación de la diferenciación celular de las células T(H) 1 y T(H) 2.
- Investigación de la expresión génica relacionada con la diferenciación T(H) 17 (por ejemplo, RORgamma t, IL21).
- Inmunoprecipitación de cromatina (ChIP) para determinar los sitios de unión de BATF en los promotores de genes diana y los elementos intergénicos.
Principales resultados:
- Los ratones Batf(-/-) muestran una diferenciación normal de las células T(H) 1 y T(H) 2 pero un defecto significativo en la diferenciación de las células T(H) 17.
- Batf(-/-) Las células T no inducen factores clave como RORgamma t e IL21 necesarios para el desarrollo de T(H) 17.
- La sobreexpresión de IL21 o RORgamma t no rescató completamente la producción de IL17 en las células T Batf.
- El BATF se une directamente a los promotores de Il17, Il21 e Il22, así como a los elementos intergénicos conservados dentro del locus Il17a-Il17f.
Conclusiones:
- Las MTD son indispensables para la diferenciación de las células T (((H) 17).
- El BATF actúa como un regulador crítico de la identidad y función de las células T(H) 17.
- Los hallazgos revelan un papel novedoso y esencial para el BATF en la orquestación de la respuesta inflamatoria mediada por las células T ((H) 17).
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