Immunofluorescence Localization of Nuclear Retinoid Receptors in Psoriasis Versus Normal Human Skin
Psoriasisresponds favourably to treatment with retinoids but the cellularpathways mediating these effects are poorly understood. Retinoidsregulate keratinocyte proliferation and maturation via binding tonuclear retinoic acid receptors (mainly RARα and RARγ) which formheterodimers with the 9-cis-RA receptor, RXRα. We have previously shownthat mRNA expression of RARα and RXRα is down-regulated in psoriaticlesions 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.