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Un precursor comprometido a las células linfoides innatas.

Michael G Constantinides1, Benjamin D McDonald1, Philip A Verhoef1

  • 1Committee on Immunology, Department of Pathology, The Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA.

Nature
|February 11, 2014
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores descubrieron una nueva célula precursora, el progenitor de células linfoides innatas (ILCP), que se define por el factor de transcripción PLZF. Este hallazgo aclara las relaciones de desarrollo entre las células linfoides innatas (ILC), las células asesinas naturales (NK) y los inductores de tejido linfoide (LTis).

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Área de la Ciencia:

  • Inmunología Inmunología.
  • Biología del desarrollo Biología del desarrollo.
  • Biología celular Biología celular.

Sus antecedentes:

  • Las células linfoides innatas (CLI) son cruciales para la inmunidad y la reparación de los tejidos, pero sus orígenes de desarrollo y sus relaciones con otros linfocitos innatos siguen sin estar claros.
  • La clasificación actual de los ILC en grupos 1, 2 y 3 se basa en perfiles de citoquinas, no en vías de desarrollo.
  • Las similitudes entre las ILC, las células asesinas naturales (NK) y los inductores de tejido linfoide (LTis) sugieren orígenes de desarrollo compartidos.

Objetivo del estudio:

  • Identificar y caracterizar nuevos precursores de las células linfoides innatas.
  • Para aclarar las vías de desarrollo y las relaciones de linaje de ILCs, células NK, y LTis.
  • Determinar el papel del factor de transcripción PLZF en la diferenciación de los linfocitos innatos.

Principales métodos:

  • Estudios de rastreo de linaje y transferencia en hígado fetal de ratón y médula ósea adulta.
  • Caracterización de una nueva población de precursores linfoides que expresan altos niveles de PLZF.
  • Análisis del desarrollo del subconjunto ILC después de la supresión de PLZF.

Principales resultados:

  • Identificación de una nueva población de precursores, las células PLZF{high}, en los órganos inmunes de ratones.
  • Las células PLZF ((alto) demostraron un potencial multipotente, dando lugar a los subconjuntos ILC1, ILC2 e ILC3.
  • La eliminación de PLZF tuvo un impacto significativo en el desarrollo del subconjunto ILC, confirmando el papel crítico de PLZF.
  • Estos precursores eran distintos de las células LTi y NK clásicas, pero incluían un subconjunto de células NK1.1(+) DX5(-) "similares a NK".

Conclusiones:

  • Establecimiento de nuevas relaciones de linaje entre las células ILC, NK y LTi.
  • Identificación del precursor común de las ILC, denominado progenitor de células linfoides innatas (ILCP).
  • Confirmación de un papel amplio y definitorio para el factor de transcripción PLZF en la diferenciación de los linfocitos innatos.