New modulated genes in psoriasis-derived keratinocyte subpopulations.

T cells play a crucial role in the pathogenesis of psoriasis, recent data emphasize the key role of keratinocytes that, by carrying intrinsic alterations, could determine the formation of skin lesions resembling psoriasis, without the participation of T-cell derived cytokines. In particular, transit amplifying (TA) cells, the stem cell progeny, seems to be responsible for the psoriatic phenotype. The aim of this study was to analyze the role of keratinocytes sub-populations in the pathogenesis of psoriasis. We analyzed the gene expression profile (GEP) of human keratinocyte sub-populations (stem, “early” TA (ETA) and “late” TA (LTA) cells), derived from healthy skin, lesional and non-lesional psoriatic skin. The total RNA samples, extracted from keratinocyte subpopulations immediately after separation, were hybridized onto the Affymetrix human U133 plus 2.0 GeneChip Array. We identified a small number of up-regulated genes (12 probe sets, corresponding to 8 genes) in keratinocyte subpopulations derived from lesional psoriasis vs. healthy and non-lesional psoriasis. We confirmed the increased expression levels of TCN1, S100A7A, KYNU, SERPINB13, FOXE1, but solely due to the keratinocyte component. We identified for the first time the up-regulation of TMEM171, CLEC7A and NDRG4, which seems to correlate with the pathophysiology of psoriasis. Moreover, GEP analysis of lesional psoriasis sub-populations, as compared to the non-lesional psoriatic counterpart revealed the modulation of 17 probe sets, corresponding to 13 genes. Among these genes, we recognized for the first time the up-regulation of IL13RA1, CCDC109B and CD47. These results indicate the importance of keratinocyte compartment in psoriasis, opening the way to the study of new genes potentially critical in the pathogenesis of psoriasis.