Autoreactive T-Cells in Psoriasis: Are They Spoiled Tregs and Can Therapies Restore Their Functions?

Psoriasis is a chronic inflammatory skin disease, which affects 2-4% of the population worldwide. T-cell derived factors such as Th17 and Th1 cytokines or cytokines such as IL-23, which favors Th17-expansion/differentiation, dominate in the disease. Therapies targeting these factors have been developed over the years. An autoimmune component is present, as autoreactive T-cells specific for keratins, the antimicrobial peptide LL37 and ADAMTSL5 have been described. Both autoreactive CD4 and CD8 T-cells exist, produce pathogenic cytokines, and correlate with disease activity. Along with the assumption that psoriasis is a T-cell-driven disease, Tregs have been studied extensively over the years, both in the skin and in circulation. This narrative review resumes the main findings about Tregs in psoriasis. We discuss how Tregs increase in psoriasis but are impaired in their regulatory/suppressive function. We debate the possibility that Tregs convert into T-effector cells under inflammatory conditions; for instance, they may turn into Th17-cells. We put particular emphasis on therapies that seem to counteract this conversion. We have enriched this review with an experimental section analyzing T-cells specific for the autoantigen LL37 in a healthy subject, suggesting that a shared specificity may exist between Tregs and autoreactive responder T-cells. This suggests that successful psoriasis treatments may, among other effects, restore Tregs numbers and functions.

Automated summary

Psoriasis is a chronic inflammatory skin disease that affects 2-4% of the global population. T-cell derived factors dominate in the disease, and therapies targeting these factors have been developed. Autoreactive T-cells specific for keratins, LL37, and ADAMTSL5 have been described, and both autoreactive CD4 and CD8 T-cells exist and correlate with disease activity. This review focuses on Tregs in psoriasis, discussing their increased numbers but impaired regulatory/suppressive function, and the possibility of conversion into T-effector cells under inflammatory conditions.