Changes in the Immune Profile and Chromatin Accessibility of Peripheral Regulatory T Cells in Psoriasis Patients Before and After Treatment With Biologics

Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti-IL-17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from 'inhibitory' to 'inflammatory' cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to INO80, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as NCAM2, CDH18, ZEB1 and CCDC22, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.