engleski

Transcriptional profiling of γδT cells in peripheral blood of psoriasis vulgaris patients

Psoriasis vulgaris is a common, immune-mediated erythematosquamous skin disease driven by infiltrating T cells. Of these, proinflammatory γδT cells expressing skin homing receptors (CLA/SELPLG, CCR6 and CCR10) are particularly enriched in psoriatic plaques, inversely mirroring diminished peripheral blood γδT cell frequency in affected individuals. Nevertheless, the molecular mechanisms underlying this trafficking remain unknown. To approach this, we studied gene expression profiles [qRT-PCR, data normalized to TBP, 2(- deltadeltaCt) method] of chemokine/selectin receptors (IL18R, CCR6, CCR10, SELPLG) and transcription factors likely controlling innate (PLZF/ZBTB16), cytotoxic/type 1 (RUNX3, EOMES, TBX21), and type 17 functions (RORC) in sorted peripheral CD3+TCRγδ+T cells (S3e sorter, 18 psoriatic, 18 healthy donors), together with serum levels of IL-17, IL-23, IL-18, CCL20 and CCL27 (Luminex 200, Procarta Plex Custom kit). The expression of ZBTB16 (median 0.62-fold change, P=0.0028, Mann-Whitney test), RORC (0.55-fold change, P=0.045), RUNX3 (0.57-fold, P=0.024), IL18R (0.6-fold change, P=0.024), and SELPLG genes (0.32-fold change, P=0.032) was significantly downregulated in blood γδT cells of psoriatic donors. ZBTB16 (Spearman’s rho=-0.39, P=0.03) and IL18R (rho=-0.38, P=0.038) mRNA abundance inversely correlated with serum CCL27 levels, and a reciprocal relationship between RORC and circulating CD3+TCRγδ+ T cell fraction (rho=-0.34, P=0.042) was noted as well. In addition, TBX21 and EOMES gene expression positively correlated with peripheral CD3+TCRγδT+ (rho=0.49, P=0.0023) and CD3+TCRγδ(hi) (rho=0.43, P=0.0097) T cell numbers, respectively. In conclusion, our findings enlighten transcriptional alterations in circulating γδT cells of psoriatic patients ; however, the analysis of skin-derived γδT cells will be necessary for detailed clarification of transcriptional rewiring underlying these processes.

Psoriasis vulgaris ; γδ T cells ; transcriptional profiling

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