engleski

Phenotyping and functional role of MAIT and γδT peripheral blood lymphocytes in the development and progression of psoriasis vulgaris

Psoriasis vulgaris (PV) is a chronic, recurrent erythematosquamous dermatosis mediated by aberrantly activated immune cells. Of these, the unconventional effectors of the innate immunity, such as CD3+TCR-Vα7.2+MAIT and γδT-lymphocytes, may have an important, yet incompletely understood role. Upon stimulation, these cells mediate rapid and robust inflammatory responses by releasing disease-driving cytokines such as IL-17, INF-y and TNF-α. Here, we have used flow cytometry and the Luminex analysis of serum IL- 17, IL-23, IL-18, CCL20 and CCL27 levels (Procarta Plex Custom kit) to establish circulating target cell frequencies and the serum cytokine and chemokine levels in relation to disease presentation. Peripheral MAIT and γδT cells from 19 patients and 19 healthy, age and sex-matched controls were immunophenotyped (FACS Canto cytometer) and sorted (S3e cell sorter) using MR1 APC-conjugated tetramers and CD3 FITC, CD4 PE/Cy7, CD8 PerCP, TCR Valpha7.2 PE and γδTCR PE/Cy7 monoclonal antibodies. Dead cells were excluded by LIVE/DEAD® viability dye, and flow cytometry data analysed with FlowLogic software. Compared to controls, PV patients had significantly lower frequency of circulating, peripheral blood CD8+T cells [median (interquartile range), 34.9 (32.2-36.4) vs 44 (37.8-50.3) %, P=0.0071, Mann-Whitney test] and double positive, CD4+CD8+(DP) MAIT cells [2.66 (1.05-4.58) vs 4 (3.22-11.31) %, P=0.023], whereas CD4+T cell frequency was significantly higher [59.2 (56.7-63.1) vs 49.8 (44.2-58.7) %, P=0.023]. Moreover, CD8+MAIT frequencies were higher in female subjects (P=0.02) and inversely correlated to CCL27 serum levels (Spearman’s ρ=-0.356, P=0.028). γδT cell abundance was unrelated to case-control status, but was positively associated with anti-CMV IgG titer (ρ=0.57, P = 0.007). In line, CMV IgG(+) subjects had higher proportion of TCRγδ(high)T cells compared to CMV IgG(-) individuals (P=0.0029). Our preliminary findings support the role of peripheral DP MAIT compartments in psoriasis and warrant further analysis of additional CD4+ and CD8+ T cell populations in larger studies, as well as the transcriptome analysis of MAIT and γδT cells for uncovering their functional characteristics in PV.

Psoriasis vulgaris ; MAIT cells ; MR1 protein ; γδ T cells

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