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La interacción del gen virus-más-susceptibilidad determina el gen de la enfermedad de Crohn Atg16L1 fenotipos en el
Ken Cadwell1, Khushbu K Patel, Nicole S Maloney
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|July 7, 2010
Resumen
Una infección viral específica que interactúa con una mutación genética de la enfermedad de Crohn desencadena problemas intestinales en ratones. Esto destaca cómo las variantes genéticas, los virus y las bacterias intestinales pueden causar fenotipos de enfermedades inflamatorias.
Área de la Ciencia:
- Gastroenterología y Gastroenterología.
- Inmunología Inmunología.
- Microbiología Microbiología.
Sus antecedentes:
- Los alelos de riesgo genético comunes para las enfermedades inflamatorias no se comprenden completamente.
- Solo una pequeña fracción de los individuos con estos alelos desarrollan enfermedades.
Objetivo del estudio:
- Investigar los mecanismos moleculares subyacentes al desarrollo de enfermedades en individuos portadores de factores de riesgo genéticos.
- Para dilucidar el papel de las interacciones de los genes de susceptibilidad al virus en la patogénesis de la enfermedad inflamatoria intestinal.
Principales métodos:
- Inducción de patologías intestinales en ratones a través de una infección por un virus específico y una mutación en el gen de susceptibilidad a la enfermedad de Crohn (Atg16L1).
- Análisis de la función celular de Paneth, los patrones de expresión génica y la respuesta a la lesión inducida por el sulfato de sodio de dextrano.
- Evaluación de las funciones de TNF-alfa, IFN-gamma y bacterias comensales en el desarrollo de la enfermedad.
Principales resultados:
- La interacción del gen de susceptibilidad al virus causó un empaque anormal de los gránulos y alteró la expresión génica en las células de Paneth.
- Esta interacción condujo a patologías que se asemejan a la enfermedad de Crohn tras una lesión química.
- Las patologías dependieron de la señalización TNF-alfa e IFN-gamma y fueron mitigadas por antibióticos de amplio espectro.
Conclusiones:
- Una infección viral específica que interactúa con la mutación del gen Atg16L1 puede inducir patologías intestinales similares a la de Crohn en ratones.
- Los fenotipos de enfermedades inflamatorias en individuos genéticamente susceptibles pueden surgir de una compleja interacción de infecciones virales, genética del huésped y factores ambientales, incluido el microbioma.
- Los hallazgos proporcionan un vínculo mecánico entre la predisposición genética, los desencadenantes virales y el desarrollo de la enfermedad inflamatoria intestinal.
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