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La amortiguación de las vías de muerte por schnurri-2 es esencial para el desarrollo de las células T
Tracy L Staton1, Vanja Lazarevic, Dallas C Jones
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Nature
|April 9, 2011
Resumen
La represión de las vías de muerte inducidas por el receptor de células T (TCR) es crítica para el desarrollo de las células T. Schnurri-2 (Shn2) amortigua la muerte inducida por TCR, evitando la selección negativa inapropiada y asegurando la diferenciación adecuada de las células T.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El desarrollo de las células T se basa en la interpretación de la señal del receptor de células T (TCR) por parte de los timocitos.
- La intensidad de la señal determina el destino del timocito: las señales altas causan la selección negativa (muerte), las señales intermedias causan la selección positiva (diferenciación).
- Se conocen reguladores de la intensidad de la señal TCR, pero los componentes específicos que definen los límites de selección no están claros.
Objetivo del estudio:
- Identificar nuevos reguladores que definan los límites entre la selección de células T positivas y negativas.
- Investigar el papel de schnurri-2 (Shn2) en la modulación de las vías de muerte inducidas por TCR durante el desarrollo de las células T.
Principales métodos:
- Estudios in vivo e in vitro con ratones genéticamente modificados (Shn2-/-).
- Análisis del destino celular del timocito, la sensibilidad a la muerte inducida por TCR y las vías de señalización.
- Evaluación del desarrollo y la diferenciación de las células T en los timocitos deficientes en Shn2.
Principales resultados:
- La deficiencia de Shn2 conduce a una selección negativa inapropiada de timocitos doblemente positivos sobre señales de selección positiva.
- Los timocitos Shn2-/- muestran una mayor sensibilidad a la muerte inducida por TCR in vitro e in vivo.
- La ablación genética de la muerte inducida por TCR rescata la selección positiva en los timocitos deficientes en Shn2.
- Shn2 actúa aguas abajo de la señalización TCR para amortiguar la vía de muerte mitocondrial inhibiendo la activación de Bax.
Conclusiones:
- Schnurri-2 (Shn2) es un regulador crucial que amortigua las vías de muerte inducidas por TCR.
- Shn2 asegura el desarrollo adecuado de las células T al prevenir una selección negativa inapropiada durante la selección positiva.
- Shn2 funciona como un punto de control crítico, equilibrando la diferenciación del timocito y la muerte.
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