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- Title
A sharp decrease of Th17, CXCR3<sup>+</sup>-Th17, and Th17.1 in peripheral blood is associated with an early anti-IL-17-mediated clinical remission in psoriasis.
- Authors
Tsiogkas, Sotirios G; Mavropoulos, Athanasios; Dardiotis, Efthimios; Zafiriou, Efterpi; Bogdanos, Dimitrios P
- 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. Psoriasis is induced by circulating pro-inflammatory cell populations and the IL-23/Th17 pathway has been arguably recognized as a crucial component for the development of the disease. In psoriasis patients receiving biologic IL-17 therapeutic blockade circulating Th1, Th17 and sub-populations as CXCR3+-Th17 and Th17.1 were decreased as early as 3 months after treatment initiation. Early anti-IL17 mediated clinical remission is accompanied by a significant decrease of specific circulating pro-inflammatory cell populations in therapy-responding patients.
- Subjects
DISEASE remission; PSORIASIS; CELL populations; CHEMOKINE receptors; BIOTHERAPY
- Publication
Clinical & Experimental Immunology, 2022, Vol 210, Issue 1, p79
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1093/cei/uxac069