Psoriasis: crucial role of LXR-α RNomics

Departmentof Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaLiver X receptor-alpha (LXR-a), being a member of the nuclear receptor/transcription factor family, has been widely recognizedto 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-a gene in cultured primary keratinocytes derivedfrom 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-a gene has an inherent capacity to regulate genes coding forinflammatory cytokines, cell cycle, immunomodulation and reactive oxygen species scavenging within human keratinocytes.Moreover, LXR-a gene knockdown within normal human keratinocytes simulated the genomic profile observed in psoriatic skinlesions. On the basis of our study, we propose that restoration of LXR-a expression/function within a psoriatic lesion may helpto switch the transition from psoriatic to symptomless skin.Genes and Immunity (2010) 11, 37–44; doi:10.1038/gene.2009.63; published online 1 October 2009Keywords: LXR-a; gene knockdown; effector genes; cell cycle; keratinocytes; psoriasis