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Dependencia de la auto tolerancia en el desarrollo dirigido por TRAF6 del estroma tímico
Taishin Akiyama1, Shiori Maeda, Sayaka Yamane
1Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Science (New York, N.Y.)
|February 12, 2005
Resumen
El factor 6 asociado al receptor del factor de necrosis tumoral (TRAF6) es crucial para la organización de las células epiteliales del timo (CET) y el mantenimiento de la auto tolerancia. Su deficiencia conduce a TECs desorganizados y puede inducir la autoinmunidad.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del desarrollo Biología del desarrollo.
- Mecanismos moleculares de las moléculas.
Sus antecedentes:
- Las células epiteliales del timo (CET) crean microambientes esenciales para el desarrollo de las células T y la auto tolerancia inmune.
- Los mecanismos moleculares que rigen la diferenciación de TEC y la compartimentación del timo siguen siendo incompletamente entendidos.
Objetivo del estudio:
- Investigar el papel del factor 6 asociado al receptor del factor de necrosis tumoral (TRAF6) en la diferenciación TEC y la organización del estroma tímico.
- Para aclarar el impacto de la deficiencia de TRAF6 en la auto tolerancia y la auto inmunidad.
Principales métodos:
- Análisis del estroma tímico en embriones con deficiencia de TRAF6 (TRAF6(-/-).
- Evaluación de la distribución y maduración del TEC medular (mTEC).
- Injerto de TRAF6 ((-/-) estroma tímico en ratones desnudos atímicos para evaluar la autoinmunidad.
Principales resultados:
- La deficiencia de TRAF6 dio lugar a una distribución desorganizada de las TEC medulares (mTEC).
- Los mTEC maduros estaban ausentes en los embriones de TRAF6.
- El injerto de TRAF6 ((-/-) estroma tímico indujo la autoinmunidad en ratones receptores.
Conclusiones:
- TRAF6 juega un papel crítico en la dirección del desarrollo y la organización del estroma tímico.
- TRAF6 es un punto regulador clave para mantener la auto-tolerancia y prevenir la autoinmunidad.
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