The contribution of keratinocytes to the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) develops from a complex interplay between environmental, genetic, immunologic and biochemical factors. Relevant to the amplification and persistence of inflammatory and immune responses in AD skin are keratinocytes, which can be induced to secrete proinflammatory mediators in response to a variety of stimuli, including epidermal barrier perturbation. Moreover, keratinocytes from AD patients synthesize exaggerated amounts of mediators (e.g., GM-CSF and RANTES/CCL5) important for enhanced recruitment as well as sustained survival and activation of T cells and dendritic cells. AD keratinocytes have a constitutive dysregulated activity of transcription factors that modulate the expression of inflammatory genes, suggesting the existence of predetermined mechanisms targeting atopic inflammation to the skin. Among these, the existence of a defective epidermal barrier, which appears related to decreased ceramide generation and abnormal degradation of corneodesmosomes, certainly plays a central role in the predisposition to AD.