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DDX55 protege la homeostasis de las células T naïves suprimiendo los elementos transponibles que promueven la

Mengyue Wu^1,2,3, Kepan Linghu^1,2, Qimin Yin^1,2,3

¹Laboratory of Epigenetics and Immunology, West China Institute of Women and Children's Health, NHC Key Laboratory of Chronobiology, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.

Science immunology

|September 5, 2025

Resumen

La DEAD-box helicasa 55 (Ddx55) mantiene la homeostasis de las células T al suprimir los elementos transponibles. Su pérdida causa inestabilidad genómica y altera la proliferación de células T, destacando Ddx55

Área de la Ciencia:

Inmunología
La genómica
Biología molecular

Sus antecedentes:

Las células T ingenuas requieren homeostasis para un grupo de células T estable y diverso, crucial para la preparación inmune.
Los mecanismos que gobiernan la homeostasis y el primado de células T no se comprenden completamente.

Objetivo del estudio:

Identificar los reguladores clave de la homeostasis de las células T ingenuas.
Aclarar los mecanismos moleculares por los cuales estos reguladores mantienen la estabilidad de las células T y evitan la activación aberrante.

Principales métodos:

Prueba genética funcional basada en el aprendizaje automático para identificar factores involucrados en la homeostasis de las células T.
Análisis de la expresión y función de la helicasa DEAD-box 55 (Ddx55) en células T naïves.
Investigación de la regulación del elemento transponible (TE) y la estabilidad genómica tras la manipulación de Ddx55.
Evaluación de la unión de MYC y su papel en la supresión de TE mediada por Ddx55.

Principales resultados:

Ddx55 fue identificado como un factor crítico para la homeostasis de células T ingenuas.
Ddx55 suprime los elementos transponibles similares a potenciadores y promotores cerca de los genes de activación de las células T.
La pérdida de Ddx55 conduce a la desrepresión de TE, la formación de bucles R y la inestabilidad genómica, interrumpiendo la homeostasis y la proliferación de las células T.
DDX55 se une directamente a MYC, impidiendo su acceso a los loci TE y la activación inadecuada de TE.

Conclusiones:

Las células T naïves utilizan DDX55 para mantener la estabilidad genómica y el equilibrio homeostático.
DDX55 actúa como un guardián crucial, previniendo la activación aberrante de las células T mediante el control de la actividad del elemento transponible.
Comprender el papel de DDX55 ofrece información sobre el mantenimiento de la integridad del grupo de células T y la preparación inmune.

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