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Las APC requieren un elemento cis-regulador distinto para instruir la tolerancia a los antígenos dietéticos
Jie Zhao1,2,3,4, Jiacheng Hao1,2,3,4, Jincheng Chen1,2,3,4
1Institute for Immunology, Tsinghua University, Beijing, China.
Nature communications
|February 21, 2026
Resumen
Un elemento regulador recientemente identificado, el OCR369, controla la expresión de RORγt en las células presentadoras de antígenos (APC), crucial para la tolerancia oral. Su deleción afecta el desarrollo de Treg, lo que lleva a una inflamación intestinal y un aumento de la susceptibilidad a las alergias.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Gastroenterología y Gastroenterología.
Sus antecedentes:
- La tolerancia oral es vital para la inmunidad intestinal, previniendo la inflamación contra los antígenos dietéticos y microbianos.
- Se sabe que las células presentadoras de antígenos que expresan RORγt (APC) promueven la tolerancia oral al inducir las células T reguladoras (Tregs).
Objetivo del estudio:
- Para identificar los mecanismos reguladores que controlan la expresión de RORγt específicamente en RORγt+ APCs.
- Para aclarar el papel de estos elementos reguladores en el mantenimiento de la homeostasis intestinal y la tolerancia oral.
Principales métodos:
- Identificación de un elemento cis-regulador (OCR369) dentro del locus del gen Rorc.
- Análisis de la interacción de OCR369 con RUNX3 y su papel en la formación del bucle de cromatina.
- Investigando los efectos de la deleción de OCR369 en RORγt+ APCs, ILC3s, Tregs y inflamación intestinal en ratones.
Principales resultados:
- La deleción de OCR369 redujo significativamente las RORγt+ APC y las ILC3 en ratones.
- Esta reducción condujo a una disminución de los RORγt+ Tregs específicos para los antígenos dietéticos y microbianos.
- La deleción de OCR369 dio lugar a una inflamación espontánea del intestino delgado y a una mayor susceptibilidad a las alergias.
Conclusiones:
- OCR369 es un regulador clave de la expresión de RORγt en RORγt+ APCs, distinto de otros tipos de células RORγt+.
- Los RORγt+ APC, regulados por el OCR369, son esenciales para la tolerancia oral y la salud intestinal.
- La desregulación de esta vía compromete la tolerancia inmune y promueve las condiciones inflamatorias.
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