engleski

The proportions of MR1-restricted TCRVa7.2+ and VcVd1-d2-TCR subtypes are altered in human psoriatic skin and vary with age

Innate-like T cells, such as cd and MR1-restricted TCRVa7.2 subsets, perform vital homeostatis functions at epithelial sites, but their pathogenic relevance in vulgar psoriasis (PV), a common autoinflammatory skin disorder, remains unclear. Here, we used flow cytometry (FACS Canto II, FlowLogic) to investigate the phenotype and numbers of MR1-restricted TCRVa7.2+ and cd T cells by examining skin samples from 26 adult PV patients and 16 healthy, age and sex-matched controls. Cell suspensions were obtained from lesional and normal skin (Whole Skin Disso- ciation Kit, gentleMACS Dissociator), and stored at -80°C before thawing and cell counting. For staining, fixable viability dye, FcR blocking reagent, MR1-5-OP-RU tetramers, CD3e, CD4, CD8a, TCRVa7.2, TCRcd, TCRVd1, and TCRVd2 monoclonal antibodies were used. As expected, CD3+T cells were more frequent in lesional skin compared to healthy-looking skin [80.6(68.3–89.1) vs. 26.5 (16.8–58) %, median (interquartile range), PV vs controls, P = 0.00008, Mann-Whitney test]. There was a marked change in composition of the cd TCR subtypes in psoriatic skin, reflecting a strong enrichment of Vd1-Vd2- cells within the cd T compartment [1.6 (1.2–3.2) vs. 1 (0.7–1.4) %, P = 0.001], followed by a decrease in Vd2+T cell abundance [0.065 (0.03–0.12) vs. 0.22 (0.05–0.5) %, P = 0.0091]. Aged lesional skin contained fewer Vd1+T cells (Spearman’s q = -0.72, P = 0.00004, n = 26), a phenomenon not observed in healthy surgical specimens. PV skin samples were also enriched in CD8+MR1-tet+TCRVa7.2+ cell numbers compared to controls [3.4 (2.2–4.7) vs 2.2 (1.4 –3.2) % of T cells, P = 0.039], more so in younger patients (q = -0.45, P = 0.021, n = 26). CD4+MR1-tet+TCRVa7.2+ T cells were rare in psoriatic plaques and appeared more readily in severely affected patients (q = 0.5, P = 0.011, n = 26), as judged by PASI. Altogether, our prelimi- nary results suggest a potential role for MAIT and cd T cell subsets in PV and warrant further analysis of their clonotypes and function

psoriasis, TCR subtypes

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