engleski

Deregulated miR-20a/miR-92b circuit underlies changes in circulating γδT cell proportions in psoriasis vulgaris

Psoriasis vulgaris (PV) is a common, autoinflammatory dermatosis driven by T cells. The role played by unconventional, innate-like γδT cell populations in PV has been less well recognised, but the next generation of multi- messenger biology provides an opportunity to break this impasse. To this end, we investigated the composition of flow-sorted γδT cells (CD3ε, panTCRγδ, TCRVδ1/δ2, FACS Canto II/BioRadS3e) in relation to their microRNA expression (hsa-miR- 20a-5p/-29a-3p/-92b-5p, qPCR, reference: hsa-miR- 423-3p, 2-ΔΔCt) by using a deeply phenotyped cohort of 12 affected and 14 control individuals. We also analyzed gene expression in bulk γδT cells (EOMES, RUNX3, TBX21, RORC, CCR6, ZBTB16, SELPLG and IL18R, qPCR, reference: TBP, 2-ΔΔCt) and serum levels of IL-17A/F, IL-18, IL-23, CCL20, and CCL27 (Luminex). Vδ1-δ2- (median 35 % vs. 17 %, P=0.039, Wilcoxon test) and Vδ1-δ2- γδTCRint compartments (40 % vs. 22 %, P=0.02) were expanded in γδT cells from PV patients. The bulk γδT cells in PV were enriched in miR-92b (FC=13.2, P=0.013), but depleted of miR-20a (FC=0.27, P=0.0014). A strong inverse relationship was also noted between miR-20a abundance and the number of Vδ1-δ2- γδTCRint cells in the blood (ρ=-0.61, P=0.0035, Spearman test). ZBTB16, SELPLG and IL18R transcripts followed miR- 20a dynamics (0.44<ρ<0.56, 0.038>P>0.0054), suggesting that cell homing and trafficking may underlie numerical evolution of certain γδT subsets in PV. In contrast, miR-92b lacked association with cell numbers. Age, sex, BMI, the burden of inflammation and CMV status had no major effect on miR-20a/92b expression in bulk γδT cells. In conclusion, we provide an updated constraint on miR-20a/29a/92b expression in purified γδT blood cells from PV donors. A further study into the cellular landscape of miRNA expression is warranted.

psoriasis, gamma-delta T cells, miR-92b, miR-20a

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