Calcipotriol and betamethasone dipropionate synergistically enhances the balance between regulatory and proinflammatory T cells in a murine psoriasis model

A topical medication combining calcipotriol (Cal) and betamethasone dipropionate (BDP) has proven effective in a number of randomized controlled trials performed in patients with psoriasis, but its mechanism of action has not been fully elucidated. We investigated whether the combination of Cal and BDP (Cal/BDP) in this topical medication had a synergistic effect on psoriasis-like dermatitis and explored the underlying immunological mechanisms in a murine psoriasis model induced by application of imiquimod. Cal/BDP synergistically inhibited ear thickening induced by imiquimod compared to monotherapy with either Cal or BDP. In addition, Cal/BDP significantly suppressed the interleukin (IL)-23/IL-17-producing T (T17) pathogenic axis, including expression of IL-17a, IL-23a, IL-22 and TNF-α mRNA in skin lesions and expansion of CCR6(+) γδ T17 cells in the draining lymph nodes. Notably, Cal/BDP synergistically induced regulatory CD8(+) T cells and also improved the balance between regulatory CD8(+) or CD4(+) T cells and proinflammatory CCR6(+) γδ T17 cells in the draining lymph nodes. These results suggest synergistic anti-psoriatic activity of Cal/BDP with normalization of the imbalance between regulatory CD8(+) or CD4(+) T cells and proinflammatory CCR6(+) γδ T17 cells, which contributes to successful control of psoriasis by Cal-BDP combination therapy.