Phenotypical analysis of ectoenzymes CD39/CD73 and adenosine receptor 2A in CD4+CD25highFoxp3+ regulatory T-cells in psoriasis

Abstract

Background

CD39 and CD73 are two novel cell surface markers of CD25^highFoxp3⁺ regulatory T-cells (Tregs). Concordant expression of these two ectoenzymes not only discriminate Tregs from other cell populations, but also generates pericellular adenosine, which has been reported to suppress proliferation of activated T effector (Teff) cells. Because it is currently unclear whether human ectoenzymes (CD39/CD73) are involved in the impaired suppressive activity of Tregs in psoriasis, we examined the frequencies and phenotypes of CD39/CD73-expressing Tregs and related receptor adenosine receptor 2A (A_2AR) in peripheral blood of patients with different types of psoriasis.

Methods

Peripheral blood mononuclear cells (PMBC) were prepared from patients with three different types of psoriasis (psoriasis vulgaris, pustular psoriasis and erythrodermic psoriasis). CD4⁺ cells were separated from PBMC by negative selection on midiMACS columns, and the frequencies and phenotypes of CD39 and CD73 expressing Tregs, and A_2AR expressing Teff were all determined by flow cytometry analysis. Blood from healthy volunteers served as controls.

Results

The expression of single CD73⁺ Tregs was markedly reduced (approximately 50%) in psoriasis vulgaris, compared to normal controls. In pustular psoriasis, the mean numbers of CD39⁺ Tregs and A_2AR⁺ Teff was significantly lower than in normal controls. Among three different types of psoriasis, CD39 expression was strikingly reduced in the blood Treg population of pustular psoriasis patients. Decreased CD73⁺ Tregs levels were observed in psoriasis vulgaris compared to pustular psoriasis and erythrodermic psoriasis.

Conclusions

The differences in the expression of CD39⁻ and CD73⁻ Tregs may be a factor in the pathogenesis of psoriasis.

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