Abolished TNF-α is crucial for the maintenance of B10 cells subsets in Psoriasis development

Abstract

Background: Psoriasis is a common chronic skin disease characterized by epidermal proliferation and inflammation. Tumor necrosis factor α (TNFα) has a high degree of pro-inflammatory and can cooperatively regulate the pathogenic effect of other cytokines. TNFα inhibitors have shown effective in treating plaque psoriasis. IL-10 is closely related to the severity of psoriasis. Regulatory B cells (Bregs) that produce IL-10 are identified as negative regulators of the immune response, also known as B10 cells. At present, the contribution of B10 cells to the pathogenesis of psoriasis is unclear. Therefore, we used gene knockout mice, combined with data analysis of clinical psoriasis patients, to explore the role of TNFα and IL-10 regulating B10 cell function in the occurrence and development of experimental psoriasis evidence for the psoriasis clinical diagnosis and treatment.Results: The plasma inflammatory cytokine levels from psoriasis patients were higher than those in healthy controls. Impaired mature and immature B10 cell subsets in the peripheral of psoriasis patients, and both B10 and B10 progenitor cells were correlated with the pathogenesis of psoriasis after Tretinoin (Vitamin A Acid, Retinoids) treatment. Through the psoriasis models in TNFα knockout and wild-type mice induced by IMQ, It was found that the psoriatic lesions in TNFα knockout mice were slighter than those in wild-type mice, and the proportion of B10 and B10 precursor cells in the spleen of TNFα knockout mice decreased before and after IMQ induction. The expression level of IL-10 in the skin tissue of the TNFα KO mice model was significantly decreased in contrast to WT control after IMQ treatment. Conclusions: Our study was to explore the effect of the imbalance between B10 cells and TNFα on the pathogenesis of psoriasis from psoriatic patients' B10 cells and B10 precursor cells, combined with the psoriatic animal model. The mechanism by which TNFα affects B10 cells and B10 progenitor cells still need further study.