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  • Title: A novel role of IL-17A in contributing to the impaired suppressive function of Tregs in psoriasis.
    Author: Liu Y, Zhang C, Li B, Yu C, Bai X, Xiao C, Wang L, Dang E, Yang L, Wang G.
    Journal: J Dermatol Sci; 2021 Feb; 101(2):84-92. PubMed ID: 33334656.
    Abstract:
    BACKGROUND: Regulatory T cells (Tregs) are crucial in maintaining T cell homeostasis and preventing autoimmune responses. Deficiencies in the suppressive function of Tregs contribute to the pathogenesis of various autoimmune diseases, such as psoriasis. However, whether IL-17A upregulation in psoriatic patients contributes to Treg dysfunction is unknown. OBJECTIVE: To explore the effect and underlying mechanism of IL-17A on the suppressive function of Tregs and to evaluate the restoration of the suppressive function of Tregs in psoriasis during anti-IL-17A (secukinumab) treatment. METHODS: In vitro suppression assays were performed with or without the addition of IL-17A to the coculture system. The release of inhibitory cytokines, including IL-10 and TGF-β, was assessed by qRT-PCR and flow cytometry. RNA-sequencing was conducted to characterize the cellular responses of Tregs. IL-17A signaling activation was analyzed by flow cytometry and immunofluorescence. Blood samples were collected from three psoriasis patients before and after secukinumab treatment. RESULTS: IL-17A blocked the suppressive function of Tregs, possibly by inhibiting the release of TGF-β and promoting the production of IFN-γ. Moreover, IL-17A activated the NF-κB signaling pathway in Tregs. Inhibition of the NF-κB pathway blocked IL-17A-induced upregulation of IFN-γ without affecting the secretion of TGF-β by Tregs. Clinical treatment in psoriasis with secukinumab restored the suppressive function and increased production of TGF-β in Tregs of psoriasis. CONCLUSION: Our study implies a crucial role of IL-17A in mediating the dysfunction of the Treg suppressive function in psoriasis. Secukinumab, which neutralizes IL-17A signaling, restored the suppressive function of Tregs to exert its antipsoriatic effect.
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