A novel role of IL-17A in contributing to the impaired suppressive function of Tregs in psoriasis

• Published in: Journal of dermatological science Vol. 101; no. 2; pp. 84 - 92
• Main Authors: Liu, Yanghe, Zhang, Chen, Li, Bing, Yu, Chen, Bai, Xiaocui, Xiao, Chunying, Wang, Lei, Dang, Erle, Yang, Luting, Wang, Gang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021
• Subjects: IFN-γ; IL-17A; Psoriasis; Secukinumab; TGF-β; Tregs; TGF-β; Secukinumab; IFN-γ; IL-17A; Psoriasis; Tregs
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2020.09.002

•IL-17A impairs the suppressive function of Tregs.•IL-17A limits the secretion of the inhibitory cytokine TGF-β in Tregs.•IL-17A phosphorylates NF-κB to promote the production of the inflammatory cytokine IFN-γ in Tregs.•Anti-IL-17A treatment with secukinumab in psoriasis restores the suppressive function of Tregs via the induction of TGF-β. 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. 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. 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. 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. 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.