A sharp decrease of Th17, CXCR3+-Th17, and Th17.1 in peripheral blood is associated with an early anti-IL-17-mediated clinical remission in psoriasis

Abstract

Psoriasis - an immune-mediated skin disease - implicates in its pathophysiology by circulating pro-inflammatory cell populations, cytokines, and their interactions with the epidermis. The direct effect of approved anti-interleukin- (IL-)17A and anti-IL-17R biologic therapy on immunophenotyping of peripheral blood mononuclear lymphocytes' (PBMCs) relative sub-population frequencies in psoriasis patients has not yet been described. Using multiparameter flow cytometry we examined T-cell subpopulations characterized by CCR6, CCR4, and CXCR3 chemokine receptor surface expression at baseline and after initiation of biologic therapy in PBMCs collected from 30 psoriasis patients. Increased CD3+CD4+CXCR3+, CD3+CD4+CCR6+CCR4+CXCR3+(CXCR3+-Th17), and CD3+CD4+CCR6+CCR4-CXCR3+(Th17.1) cell populations were observed in patients with psoriasis in comparison to healthy individuals (n=10). IL-17 therapeutic blockade decreased CD3+CD4+CCR6+, CD3+CD4+CXCR3+, CD3+CD4+CCR6-CXCR3+(Th1), CD3+CD4+CCR6+CCR4+(Th17), CD3+CD4+CCR6+CCR4+CXCR3+(CXCR3+-Th17), and CD3+CD4+CCR6+CCR4-CXCR3+(Th17.1) cell populations in responding psoriasis patients. Moreover, CD3+CD4-CCR6+, CD3+CD4-CXCR3+, CD3+CD4-CCR6+CCR4+(Tc17), and CD3+CD4-CCR6-CXCR3+(Tc1) percentages were also inhibited. Modulation of the same cell sub-populations was also assessed in patients treated with methotrexate (n=4), apremilast (n=4), and anti-IL-23 biologic treatment (n=4). In our study, the levels and functional capacity of peripheral pro-inflammatory Th1, Th17, and additional CCR6+T cell sub-gated populations from psoriasis patients that were treated with anti-IL-17 or anti-IL-17R targeted biologic therapy were explored for the first time. Our data clearly demonstrate that early anti-IL-17 mediated clinical remission is accompanied by a significant decrease of Th1, Th17, CXCR3+-Th17, and Th17.1 cells.