Abstract
Topical corticosteroid is a widely used for treatment of psoriasis. However, its long-term use may bring about resistance to the treatment. We have previously shown that multiple drug resistance 1 (MDR1)-expressing T cells infiltrate in the skin lesions of psoriasis, especially at the skin treated with a corticosteroid. Corticosteroids are a substrate of MDR1, and possible association of MDR1+ T cells and corticosteroid resistance has been documented in some diseases. Since MDR1+ T cells in psoriatic skin include a large number of IL-17A and IL-22-producing cells, they can be associated with corticosteroid resistance. In this study, we sought to clarify whether the blockade of IL-17A by Secukinumab affects MDR1 expression. We analyzed stocked T cells expanded by IL-2 and anti-CD3/CD28 mAb-coated microbeads from biopsy specimens taken from the skin of 7 patients treated with topical corticosteroid and from the skin of 6 patients treated with Secukinumab. The function of MDR1 was investigated by Rh123 efflux assay. Rh123low cells expressed ABCB1 gene, while Rh123hi cells did not. In addition, verapamil, a specific inhibitor of MDR1 depressed the efflux of Rh123 at 94.0±2.3 percent, and thus, we considered Rh123low cells as MDR1+ cells. In vitro treatment of a corticosteroid significantly increased the frequency of MDR1+ cells (P=0.02). The frequency of MDR1+ T cells was significantly higher in the corticosteroid-treated skin than in Secukinumab-treated patients’ skin (P=0.01). Notably, this difference was more apparent in CD4+ T cells than in CD8+ T cells. Our results suggest that, unlike corticosteroid-treated skin, MDR1+ T cells do not accumulate in the skin of Secukinumab-treated patients. While anti-IL-17A mAb more strongly improves psoriasis than do topical corticosteroids, it renders remaining skin T cells susceptible to corticosteroid treatment.
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