The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches

• Main Authors: Naoko Kanda, Toshihiko Hoashi, Hidehisa Saeki
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Journal of Clinical Medicine
• Subjects: psoriasis; regulatory T cell; forkhead box protein 3; short chain fatty acid; butyrate; interleukin-17A
• Online Access: https://www.mdpi.com/2077-0383/10/17/3880

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4⁺CD25⁺ forkhead box protein 3 (Foxp3)⁺ regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing <i>Foxp3</i> expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, <i>Bacteroidetes,</i> and <i>Faecallibacterium</i>, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis.