engleski

An altered distribution of MR1-restricted mucosal- associated invariant T cells (MAIT) in blood and skin of vulgar psoriasis patients

The unconventional MR1-restricted mucosal- associated invariant T (MAIT) cells seed multiple epithelial tissues, and in case of injury, or antigen encounter via semi-invariant TCRVα7.2 receptor, exhibit rapid effector responses. Opposite to their homeostatic functions, the peripheral blood MAIT cells were recently implicated in psoriasis vulgaris (PV) immunopathology, but the role of their skin counterparts in PV remains less well understood. To this end, we used case-control settings (54 PV patients and 21 healthy controls), serum proteomics (Luminex ProcartaPlex Immunoassays: CCL27, IL-18, IL22, CXCL9, CCL20, IFNγ, IL-10, IL- 17A, TNFα, IL-6) and flow cytometry (CD3ε, CD4, CD8a, TCRVa7.2, MR1-5-OP-RU tetramers ; FACS Canto II, FlowLogic) of peripheral blood mononuclear cells and coeval skin biopsies (gentleMACS Dissociator-assisted homogenisation, Whole Skin Dissociation Kit) to assess blood and skin MAIT cell landscape in PV. Compared to healthy skin, psoriatic lesions were enriched in CD3+ (P=0.0003, Mann-Whitney test) and CD4+ T cells (P=0.0013), whereas frequency of atypical, CD8+MR1- tet+TCRVα7.2- and CD4-CD8-MR1-tet+TCRVα7.2- MAIT subpopulations was diminished, and inversely related to increased CCL20 serum levels (ρ=-0.456, P=0.0005 ; ρ=-0.449, P=0.0006). In circulating MAIT cell comparisons, a minor, CD4+CD8+MR1- tet+TCRVα7.2+ MAIT cell compartment was reduced (P=0.0253) in PV, while more common, CD4-CD8-MR1- tet+TCRVα7.2+ (ρ=-0.466, P=0.0004) and CD8+MR1- tet+TCRVα7.2+ (ρ=-0.443, P=0.0008, ρ=-0.443, P=0.0076) peripheral MAIT cell fractions, decreased with age and high serum hsCRP levels. Finally, higher circulating IL-18 (P=0.0297), CCL20 (P=0.0129), and TNF-alpha (P=0.0116) levels were observed in PV compared to healthy controls. Overall, we describe differential distribution of MAIT cell compartments in blood and psoriatic skin, which warrants further characterization of their phenotypic, functional, and transcriptomic differences.

psoriasis, MAIT cells, serum proteomics

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