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Los metabolitos microbianos controlan el desarrollo tímico de las células T invariantes asociadas a la mucosa

François Legoux¹, Déborah Bellet², Celine Daviaud^3,4

¹INSERM U932, PSL University, Institut Curie, Paris 75005, France. olivier.lantz@curie.fr francois.legoux@curie.fr.

Science (New York, N.Y.)

|August 31, 2019

Resumen

Los metabolitos de las bacterias comensales, específicamente el 5- ((2-oxopropilidenamino) -6-d-ribitylaminouracil (5-OP-RU), son cruciales para el desarrollo de células T invariantes asociadas a la mucosa (MAIT) en el timo. Esto pone de relieve un nuevo vínculo entre la microbiota intestinal y la maduración de las células inmunes.

Área de la Ciencia:

Inmunología
Microbiología
Biología de las células T

Sus antecedentes:

El papel de la microbiota en la modulación de las funciones inmunes no se comprende completamente.
Las células T invariantes asociadas a la mucosa (MAIT) están involucradas en la homeostasis de la mucosa y están ausentes en condiciones libres de gérmenes.

Objetivo del estudio:

Investigar cómo las bacterias comensales influyen en el desarrollo de las células MAIT dentro del timo.
Identificar los componentes y mecanismos bacterianos específicos implicados en el desarrollo de las células MAIT.

Principales métodos:

Estudió el desarrollo celular MAIT en modelos murinos, incluidos ratones libres de gérmenes.
Investigó el requisito de expresión bacteriana de RibD y el antígeno MAIT 5-OP-RU.
Rastreó la migración de 5-OP-RU desde las superficies mucosas al timo y su interacción con MR1.

Principales resultados:

Se descubrió que las bacterias comensales regulan el desarrollo de células MAIT intratímicas, ya que las células MAIT no recirculan hacia el timo.
El desarrollo celular de MAIT requiere la expresión de RibD bacteriana, lo que lleva a la producción del antígeno 5-OP-RU.
El metabolito 5-OP-RU viaja al timo, se une al MR1 y promueve la expansión de los precursores celulares MAIT.

Conclusiones:

Un metabolito derivado de la microbiota (5-OP-RU) es esencial para el desarrollo intratímico de las células MAIT.
Este proceso demuestra que los metabolitos microbianos pueden controlar directamente el desarrollo de poblaciones específicas de células T.
Los hallazgos difuminan las líneas entre los antígenos microbianos exógenos y los autoantígenos en el desarrollo inmune.

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