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Las células B reguladoras controlan la autoinmunidad de las células T a través de interacciones congénitas
Ayumi Yoshizaki1, Tomomitsu Miyagaki, David J DiLillo
1Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature
|October 16, 2012
Resumen
Las células B reguladoras (células B10) que producen interleucina-10 (IL-10) pueden suprimir las enfermedades autoinmunes. Las interacciones de las células T y la IL-21 son cruciales para la función de las células B10, ofreciendo nuevas terapias potenciales.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- La autoinmunidad es autoinmunidad.
Sus antecedentes:
- Las células B son reguladores clave de las respuestas inmunes, principalmente a través de la producción de anticuerpos.
- Ciertos subconjuntos de células B, conocidos como células B reguladoras (células B10), pueden suprimir las respuestas inmunes mediante la secreción de interleucina-10 (IL-10).
- Las células B10 son potentes reguladores de las enfermedades autoinmunes dependientes de las células T en ratones, pero su regulación in vivo no se entiende completamente.
Objetivo del estudio:
- Para investigar los mecanismos que controlan la producción de IL-10 en las células B10 y la regulación inmune in vivo.
- Explorar el potencial de las células B10 expandidas ex vivo como estrategia terapéutica para enfermedades autoinmunes.
Principales métodos:
- Utilizó un modelo de ratón de esclerosis múltiple para estudiar la función celular B10.
- Investigó las funciones de las interacciones de las células T dependientes de IL-21 y CD40 en la maduración de las células B10.
- Se realizó expansión ex vivo de las células B10 utilizando señales de los receptores CD40 e IL-21.
- Se transfirieron células B10 expandidas a ratones con enfermedad autoinmune establecida.
Principales resultados:
- La maduración de las células B10 en células efectoras secretoras de IL-10 requiere interacciones congénitas de células T dependientes de IL-21 y CD40.
- La expansión ex vivo de las células B10 utilizando las señales de los receptores CD40 e IL-21 dio como resultado un aumento de cuatro millones de veces.
- La transferencia adoptiva de células B10 expandidas inhibió significativamente los síntomas de la enfermedad autoinmune en ratones.
Conclusiones:
- Las interacciones entre la IL-21 y las células T son críticas para el desarrollo y la función de las células B10 productoras de IL-10 in vivo.
- La expansión ex vivo y la reinfusión de células B10 autólogas representan un enfoque terapéutico prometedor para enfermedades autoinmunes graves.
- Esta estrategia puede ofrecer un nuevo tratamiento para enfermedades autoinmunes resistentes a las terapias actuales.
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