Keratinocytes from atopic dermatitis patients produce increased amounts of GM-CSF

Atopic diseases are characterized by important dysregulations in the production of cytokines involved in the control of immune responses. In order to examine the contribution of epidermis to the pathogenesis of atopic dermatitis (AD), keratinocyte cultures were established from uninvolved skin of patients with AD and from healthy subjects, and compared in terms of GM-CSF production. Second- or third-passage cultured atopic keratinocytes exhibited a markedly increased GM-CSF release compared to keratinocytes from healthy controls, both spontaneously and after treatment with PMA. In parallel, RT-PCR analysis showed a higher constitutive as well as PMA-induced GM-CSF gene expression in atopic keratinocytes. Moreover, keratinocyte supernatants were able to reproduce the y of hrGM-CSF on immunophenotypical and functional maturation of peripheral blood monocytes to dendritic cells. An exaggerated production of GM-CSF by atopic keratinocytes may contribute relevantly to the chronicity of AD lesions, in particular to the increased recruitment, sustained activation and enhanced antigen-presenting-cell functions of dendritic cells in AD skin.