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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
La proteína quinasa C-theta media una retroalimentación negativa sobre la función reguladora de las células T
Alexandra Zanin-Zhorov1, Yi Ding, Sudha Kumari
1Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Science (New York, N.Y.)
|March 27, 2010
Resumen
La proteína quinasa C-theta (PKC-theta) inhibe la función reguladora de las células T (Treg). El bloqueo de PKC-theta mejora la actividad de Treg, ofreciendo un potencial terapéutico para las enfermedades inflamatorias mediante la restauración de la función de Treg en presencia de citoquinas inflamatorias.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Investigación de la inflamación Investigación de la inflamación.
Sus antecedentes:
- Las células T reguladoras (Tregs) controlan las respuestas inmunes, pero son inhibidas por el factor de necrosis tumoral alfa (TNF-alfa).
- La proteína quinasa C-theta (PKC-theta) es crucial para la activación de las células T efectoras (Teff).
- El papel de PKC-theta en la función de Treg no estaba claro anteriormente.
Objetivo del estudio:
- Investigar el papel de PKC-theta en la función Treg y su interacción con el TNF-alfa.
- Para determinar si la inhibición de PKC-theta puede restaurar la actividad de Treg.
Principales métodos:
- Estudió la localización de PKC-theta en la sinapsis inmunológica Treg.
- Utilizó el bloqueo de PKC-theta en modelos in vitro e in vivo.
- Función Treg evaluada en presencia de TNF-alfa y en modelos de enfermedades.
Principales resultados:
- PKC-theta fue secuestrado lejos de la sinapsis inmunológica Treg.
- El bloqueo de PKC-theta mejoró la supresión mediada por Treg.
- Inhibición de los Treg protegidos por PKC-theta por la inactivación inducida por el TNF-alfa.
- Función Treg restaurada en pacientes con artritis reumatoide y mejor protección contra la colitis en ratones.
Conclusiones:
- La PKC-theta actúa como un inhibidor de la función Treg.
- Dirigirse a PKC-theta puede superar la inhibición inflamatoria de las citoquinas de los Tregs.
- La inhibición de PKC-theta representa una estrategia terapéutica prometedora para las enfermedades inflamatorias.
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