Immunofluorescence Localization of Nuclear Retinoid Receptors in Psoriasis Versus Normal Human Skin.

Psoriasis responds favourably to treatment with retinoids but the cellular pathways mediating these effects are poorly understood. Retinoids regulate keratinocyte proliferation and maturation via binding to nuclear retinoic acid receptors (mainly RARα and RARγ) which form heterodimers with the 9-cis-RA receptor, RXRα. We have previously shown that mRNA expression of RARα and RXRα is down-regulated in psoriatic lesions as compared with non-lesional human skin. In the present study, we investigated the protein expression of RARα, RARγ and RXRα in normal and psoriatic skin using indirect immunofluorescence analysis. Epidermal keratinocytes of normal and non-lesional psoriatic skin displayed similar nuclear localization of all three receptors; RARα was detected with decreasing intensity from basal to suprabasal layers, RARγ showed the opposite trend, whereas RXRα was evenly expressed throughout the epidermis. In lesional psoriatic skin, however, all three receptor proteins showed a much higher staining intensity in the lower half of the epidermis; in particular, RARα immunoreactivity was low or even absent in the upper layers of epidermis. The results support the idea that psoriasis is associated with abnormal retinoid signalling in lesional epidermis. [ABSTRACT FROM AUTHOR]