Psoriasis: crucial role of LXR-alpha RNomics

Liver X receptor-alpha (LXR-alpha), being a member of the nuclear receptor/transcription factor family, has been widely recognized to have a pleiotropic effect in the regulation of genes involved in innate immunity, inflammation and cholesterol homeostasis. Keeping in view the fact that psoriasis is a chronic, inflammatory and autoimmune disease with a high turnover of keratinocytes, this study was addressed to understand the functional RNomics of the LXR-alpha gene in cultured primary keratinocytes derived from skin biopsies of human psoriatic lesions, and from symptomless skin of psoriatic patients and clinically healthy subjects. The results of this study revealed for the first time that the LXR-alpha gene has an inherent capacity to regulate genes coding for inflammatory cytokines, cell cycle, immunomodulation and reactive oxygen species scavenging within human keratinocytes. Moreover, LXR-alpha gene knockdown within normal human keratinocytes simulated the genomic profile observed in psoriatic skin lesions. On the basis of our study, we propose that restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.