638 Photochemotherapy limits Treg plasticity and restores Treg function in psoriasis patients

Phototherapy is used to treat psoriasis, although the mechanisms of therapeutic effects remain unclear. The pathogenesis of psoriasis might be an imbalance of T helper 17 cells (Th17) and regulatory T cells (Treg). Recent findings suggest that Foxp3+ Treg have functional and phenotypic plasticity, and secrete proinflammatory cytokines. CD4+CD25+Foxp3+ T cells are categorized as activated Treg (aTreg: CD4+CD25+CD45RA-Foxp3high), resting Treg (rTreg: CD4+CD25+CD45RA+Foxp3low), or non-suppressive T cells (non-Treg: CD4+CD25+CD45RA-Foxp3low). Non-Treg become IL17-producing cells. We hypothesized that phototherapy affects Treg plasticity and function. In this study, we examined Treg function and the effect of bath-psoralen UVA (PUVA) therapy on these three Foxp3+ subsets and Th17. We enrolled 15 patients with psoriasis and 11 healthy controls. We evaluated the three Foxp3+ subsets and the Th17 ratio in the peripheral blood before and after every 5th bath-PUVA treatment, and after 20 bath-PUVA treatments. The ability of Treg to suppress psoriatic cell proliferation was examined with flow cytometry after bath-PUVA therapy. The rTreg and aTreg levels tended to increase after bath-PUVA therapy. Although non-Treg levels did not change after every 5th bath-PUVA treatment, non-Treg levels in 9 patients decreased after 20 bath-PUVA treatments. The Treg functional ratio was lower in psoriasis patients (70.1±25.1%) than in the age-matched controls (94.4±4.28%), and bath-PUVA therapy restored Treg function (88.1±6.47%). Increased Th17 levels decreased from 5.66±3.15% to 2.96±2.89%. These findings indicate that Treg are dysfunctional in psoriasis patients and bath-PUVA therapy restores Treg function. Bath-PUVA therapy decreases non-Treg and Th17 levels in psoriasis patients, suggesting that bath-PUVA therapy limits non-Treg plasticity to become IL17-producing T cells and directs non-Treg to aTreg.