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Los oxisteroles dirigen la migración de las células B a través de EBI2.

Changlu Liu1, Xia V Yang, Jiejun Wu

  • 1Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA. cliu9@its.jnj.com

Nature
|July 29, 2011
PubMed
Resumen
Este resumen es generado por máquina.

Los oxisteroles, como el 7α,25-dihidroxicolesterol, se identifican como ligandos endógenos para el receptor EBI2, controlando la migración de las células B y las respuestas inmunes. Este descubrimiento revela un nuevo papel para los oxisteroles en el sistema inmunológico.

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Área de la Ciencia:

  • Inmunología Inmunología.
  • Biología Molecular Biología Molecular
  • El metabolismo del colesterol.

Sus antecedentes:

  • EBI2 (GPR183) es un receptor huérfano acoplado a la proteína G crucial para la migración de las células B y la producción de anticuerpos.
  • Los oxisteroles influyen en las respuestas inmunes y el metabolismo del colesterol, principalmente a través de los receptores de hormonas nucleares.

Objetivo del estudio:

  • Para identificar los ligandos endógenos para el EBI2.2.
  • Para aclarar el papel de los oxisteroles en las funciones inmunes mediadas por EBI2.

Principales métodos:

  • Aislamiento de oxisteroles de extractos de bazo de cerdo.
  • Ensayos de migración in vitro utilizando células que expresan EBI2 y células deficientes.
  • Estudios in vivo en ratones con deficiencia de EBI2 y la inhibición de CYP7B1.

Principales resultados:

  • 7α,25-dihidroxicolesterol (OHC) identificado como un potente ligando endógeno para EBI2 (Kd = 450 pM).
  • 7α,25-OHC estimula la migración dependiente de EBI2 de las células B y T in vitro.
  • In vivo, la deficiencia de EBI2 o la desensibilización de 7α,25-OHC deteriora el homing de las células B a los folículos esplénicos.

Conclusiones:

  • Establece un vínculo directo entre EBI2 y los oxisteroles, específicamente 7α,25-OHC.
  • Descubre un nuevo papel para los oxisteroles como moléculas de señalización en el tráfico de células inmunes mediado por EBI2.
  • Destaca una nueva vía que regula las respuestas inmunes y la localización de las células B dentro de los órganos linfoides.