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Cells ; 8(10)2019 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-31569343

RESUMEN

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Células Dendríticas/inmunología , Inmunoglobulina E/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Oligodesoxirribonucleótidos/administración & dosificación , Ovalbúmina/efectos adversos , Hipersensibilidad Respiratoria/tratamiento farmacológico , Adyuvantes Inmunológicos/farmacología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inmunoglobulina E/efectos de los fármacos , Ratones , Factor 88 de Diferenciación Mieloide/genética , Oligodesoxirribonucleótidos/farmacología , Hipersensibilidad Respiratoria/inducido químicamente , Hipersensibilidad Respiratoria/metabolismo , Transducción de Señal/efectos de los fármacos
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