The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-alpha/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)-beta 1 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 Foxp3 expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-beta 1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, Bacteroidetes, and Faecallibacterium, 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.

Automated summary

Psoriasis is characterized by an imbalance in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and alterations in gut microbiota. Therapeutic agents targeting Tregs, such as anti-IL-23 or anti-IL-17A antibodies, retinoids, and probiotics/prebiotics, show promise in restoring Treg function and alleviating psoriasis symptoms.