engleski

The γδhi and γδint T cell subsets are disproportionally altered in blood and skin of vulgar psoriasis patients

Innate-like, γδT cells perform vital homeostatic, regenerative, and antimicrobial functions at barrier sites by releasing cytokines such as IL- 17, INFγ and TNFα. Their diversity, distribution and trafficking in psoriasis, an autoinflammatory skin disease, is however, less well understood. To this end, we combined serum proteomics (Luminex ProcartaPlex Immunoassays: CCL27, IL-18, IL22, CXCL9, CCL20, IFNγ, IL-10, IL-17A, TNFα, IL-6) with flow cytometry (CD3ε, panTCRγδ, TCRVδ1+TCRVδ2, FACS Canto II, FlowLogic) by using peripheral blood mononuclear cells (gradient density centrifugation) and coeval skin biopsies (gentleMACS Dissociator-assisted homogenisation, Whole Skin Dissociation Kit) from 59 PV patients (median PASI=15.2) and 27 sex-, and age-matched healthy controls (HC). In case-control comparisons, Vδ1-Vδ2-γδint compartment was significantly expanded in circulating γδT cells of the psoriatic patients (P=0.000017), leading to contraction of the Vδ1-Vδ2+γδhi (P=0.006) and Vδ1+Vδ2- γδhi subpopulation of the CD3+ T cells (P= 0.016). CD3+T cells were highly enriched in psoriatic plaques compared to healthy-looking skin (P=0.00006). Despite a net increase in cell numbers, γδTCR+ subpopulation occupied a similar fraction of the CD3+ compartment but was differently composed, reflecting a disproportional accumulation of the Vδ1-Vδ2- γδhi cells (P=0.0069), mostly at the expense of Vδ1-Vδ2+γδint cells (P=0.0019). Aged psoriatic skin contained fewer γδint (ρ=-0.351, P=0.013), in particular Vδ1-Vδ2+γδint (ρ=-0.283, P=0.049) and Vδ1+Vδ2- γδint cells (ρ=-0.471, P=0.0064). By contrast, Vδ1-Vδ2-γδhi density, which increased in response to higher serum CXCL9 (ρ=0.327, P=0.018) and hsCRP (ρ=0.529, P=0.0022), inversely mirrored serum IL- 18 (ρ=-0.467, P=0.00049), IFNγ (ρ=-0.476, P=0.00036) and TNFα levels (ρ=-0.374, P=0.0062). Overall, higher circulating IL-18 (P=0.0088) and CCL20 levels (P=0.013) were observed in PV compared to healthy controls ; the reverse was true for CCL27 (P=0.028). Altogether, we describe an altered landscape of circulating and skin γδT cell subsets in PV, providing an updated constrain for further phenotypic and functional analyses.

psoriasis ; serum cytokines ; γδT cells

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