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La citoquina TSLP de la dermatitis atópica derivada de las células epiteliales activa las neuronas para inducir la
Sarah R Wilson1, Lydia Thé, Lyn M Batia
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|October 8, 2013
Resumen
Los investigadores descubrieron que las células epiteliales liberan linfopoyetina del estroma del timo (TSLP) para activar directamente las neuronas sensoriales, causando picazón en la dermatitis atópica (DA). Esta liberación de TSLP está regulada por la vía del calcio ORAI1/NFAT en las células de la piel.
Área de la Ciencia:
- Inmunología Inmunología.
- La neurociencia es la neurociencia.
- Dermatología Dermatología dermatología.
Sus antecedentes:
- La dermatitis atópica (DA) es una enfermedad inflamatoria crónica de la piel que afecta al 10% de la población.
- La EA grave puede conducir a asma y rinitis alérgica, una progresión denominada "marcha atópica".
- La señalización de la linfopoyetina del estroma tímico (TSLP, por sus siglas en inglés) está implicada en la patogénesis de la EA y en la marcha atópica.
Objetivo del estudio:
- Para investigar el papel del TSLP derivado de células epiteliales en la mediación de la picazón en la dermatitis atópica.
- Identificar los mecanismos moleculares que regulan la liberación de TSLP de las células epiteliales de la piel.
- Para aclarar los objetivos neuronales de TSLP en la promoción de comportamientos de picazón.
Principales métodos:
- Se investigó la liberación de TSLP de los queratinocitos.
- Utilizó imágenes de calcio para estudiar la vía ORAI1/NFAT en los queratinocitos.
- Examinó los efectos de TSLP en las neuronas sensoriales, específicamente las neuronas TRPA1-positivas.
- Evaluó los comportamientos de picazón en respuesta a la estimulación TSLP.
Principales resultados:
- Las células epiteliales se comunican con las neuronas sensoriales cutáneas a través de TSLP para inducir la picazón.
- La vía de señalización de calcio ORAI1/NFAT es esencial para la liberación de TSLP de los queratinocitos.
- TSLP activa directamente un subconjunto de las neuronas sensoriales TRPA1-positivas, lo que desencadena el picor.
- Esta vía contribuye a las respuestas inflamatorias tanto en la piel como en las vías respiratorias.
Conclusiones:
- Se ha identificado un nuevo mecanismo de señalización de la picazón en la dermatitis atópica que implica la comunicación epitelial-neuronal a través de TSLP.
- La vía ORAI1/NFAT regula la liberación de TSLP, vinculando la señalización de calcio a la picazón.
- Dirigirse a TSLP o sus vías de señalización puede ofrecer estrategias terapéuticas para la dermatitis atópica y la marcha atópica.
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