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NRROS regula negativamente las especies reactivas de oxígeno durante la defensa del huésped y la autoinmunidad

Rajkumar Noubade¹, Kit Wong², Naruhisa Ota²

¹1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Maryland 20852, USA (P.A.V.).

|April 18, 2014

Resumen

Una proteína recién descubierta, el regulador negativo de ROS (NRROS), controla la producción de especies reactivas del oxígeno (ROS) en los fagocitos. La deficiencia de NRROS mejora la defensa contra los patógenos, pero corre el riesgo de daños autoinmunes, revelando un regulador clave de las respuestas inmunes.

Área de la Ciencia:

Inmunología Inmunología.
Biología celular Biología celular.
La bioquímica es la bioquímica.

Sus antecedentes:

Las especies reactivas de oxígeno (ROS) derivadas de fagocitos son cruciales para la defensa del huésped contra los patógenos.
La producción desregulada de ROS contribuye a la enfermedad granulomatosa crónica y al daño inflamatorio del tejido.
La regulación estricta de las ROS es esencial para equilibrar la inmunidad y prevenir la autoinmunidad.

Objetivo del estudio:

Identificar y caracterizar nuevos reguladores de la producción de ROS en los fagocitos.
Para aclarar el mecanismo por el cual los NRROS controlan la generación de ROS.
Investigar el papel fisiológico de los NRROS en la defensa del huésped y las enfermedades inflamatorias.

Principales métodos:

Identificó y caracterizó una nueva proteína, el regulador negativo de ROS (NRROS).
Se utilizaron fagocitos con deficiencia de NRROS y modelos de ratón knockout.
Investigó la función de las RORN utilizando ensayos bioquímicos y estudios de localización celular.
Examinó la interacción entre las subunidades NRROS y NOX2 en el retículo endoplasmático.

Principales resultados:

NRROS limita la generación de ROS por los fagocitos durante la inflamación.
Los fagocitos con deficiencia de NRROS exhiben una mayor producción de ROS y una mayor actividad bactericida.
Los ratones que carecen de NRROS muestran una mayor susceptibilidad a las enfermedades autoinmunes debido al daño oxidativo.
NRROS interactúa con NOX2 y promueve su degradación a través de la degradación ER-asociada.

Conclusiones:

NRROS es un nuevo regulador negativo de la producción de ROS de fagocitos.
NRROS juega un papel crítico en el equilibrio de la defensa del huésped y la prevención de daños en los tejidos autoinmunes.
Dirigirse a los NRROS puede ofrecer estrategias terapéuticas para enfermedades infecciosas e inflamatorias.

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