Does therapeutic intervention in atopic dermatitis normalize epidermal Notch deficiency

摘要: This viewpoint presents a unifying concept for the treatment of atopic dermatitis (AD) that is based on improvement deficient Notch signalling, which appears to represent fundamental epithelial defect AD resulting in epidermal and immunological barrier dysfunction. One study patients demonstrated marked deficiency receptors several mouse models with genetically suppressed signalling exhibit dry skin, signs scratching, skin abnormalities, increased transepidermal water loss Th2 cell-mediated changes closely resembling human AD. critically involved differentiation regulatory T cells, feedback inhibition activated innate immunity, repression activating protein-1 (AP-1), regulation late associated filaggrin- stratum corneum lipid processing, aquaporin 3- claudin-1 expression keratinocyte-mediated release thymic stromal lymphopoietin (TSLP), promotes Th2-driven immune responses TSLP- IL-31-mediated stimulation cutaneous sensory neurons induction itch. Translational evidence will be provided all major therapeutic regimens employed such as glucocorticoids, calcineurin inhibitors UV radiation may converge upregulation impaired proposed pathogenic