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La hipoxia regula el equilibrio Th17/Treg alterando la accesibilidad de la cromatina y la expresión génica
Mariana Cázares-Olivera1, Shiyang Song2,3,4, Sofia Ylinen1
1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Finland.
The FEBS journal
|December 24, 2025
Resumen
La hipoxia altera la accesibilidad de la cromatina en las células T helper, promoviendo un cambio de las células T reguladoras (Tregs) a las células T helper 17 (Th17). Este hallazgo revela nuevos mecanismos que influyen en el desarrollo de enfermedades inflamatorias.
Área de la Ciencia:
- Inmunología
- Biología Molecular
- Biología Celular
Sus antecedentes:
- La hipoxia es crucial en la inflamación e impacta el equilibrio de las células T helper 17 (Th17) y las células T reguladoras (Treg), contribuyendo a las enfermedades inflamatorias.
- El factor de transcripción factor 1-alfa inducido por hipoxia (HIF-1α) promueve la diferenciación de Th17, pero el efecto de la hipoxia en la accesibilidad de la cromatina de las células Th17 y Treg sigue sin estar claro.
Objetivo del estudio:
- Investigar cómo la hipoxia altera la accesibilidad de la cromatina en las células Th17 y Treg.
- Correlacionar estos cambios con las alteraciones transcriptómicas que afectan el equilibrio Th17/Treg.
Principales métodos:
- Ensayo de transposición de cromatina accesible mediante secuenciación (ATAC-seq) para evaluar la accesibilidad de la cromatina.
- Secuenciación de ARN (RNA-seq) para analizar los perfiles de expresión génica.
- Análisis integrado de datos ATAC-seq y RNA-seq.
Principales resultados:
- La hipoxia alteró significativamente la expresión génica en las células Treg más que en las células Th17, con un aumento de la expresión de Hif1a.
- El aumento del transductor de señal y activador de transcripción 3 (STAT3) de ARNm y proteína en las Tregs sugiere un nuevo mecanismo regulador hipoxia-STAT3.
- Se identificaron factores de transcripción (ETS1, IRF1, RUNX2, ATF3) como moduladores potenciales de la diferenciación de las células T helper en hipoxia.
- La hipoxia aumentó la accesibilidad de la cromatina en loci clave, favoreciendo la diferenciación de las células Th17 y alterando el equilibrio Th17/Treg.
Conclusiones:
- La hipoxia modula el equilibrio Th17/Treg alterando la accesibilidad de la cromatina y la expresión génica de factores de transcripción.
- Este estudio proporciona información sobre cómo la hipoxia influye en la diferenciación de Treg y contribuye a las condiciones inflamatorias.
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