Disrupted B-Cell Cytokine Homeostasis in Psoriasis: The Impact of Elevated IL-6 and Impaired IL-10 Production

Abstract

Psoriasis is a chronic inflammatory skin disease driven by immune dysregulation. This study explores the role of B cells, particularly cytokine-producing subsets, in psoriasis pathogenesis. Although T cells, particularly Th17, have been well documented in psoriasis, recent evidence suggests that B cells contribute to the disease process. Flow cytometry analysis of 50 psoriasis patients and 20 healthy controls revealed a significant increase in IL-6–producing effector B cells (Beffs) and a decrease in IL-10–producing regulatory B cells (Bregs) in psoriasis patients. As IL-6 is pro-inflammatory and IL-10 is anti-inflammatory, this imbalance likely exacerbates inflammation in psoriasis. The study also examined the effects of guselkumab, an IL-23 inhibitor, on cytokine-producing B cells. The frequency of IL-6–producing Beffs in the blood was significantly (p < 0.05) elevated in patients with psoriasis compared with that in healthy controls. In contrast, the frequency of IL-10–producing Bregs in the blood was significantly (p < 0.05) decreased in patients with psoriasis compared with that in healthy controls. In 10 biologic-naïve psoriasis patients, guselkumab significantly reduced IL-6–producing Beffs 4 weeks posttreatment, corresponding with a marked decrease in the Psoriasis Area and Severity Index (PASI). However, IL-10–producing Bregs showed no significant change over this period, suggesting that regulatory B cell recovery may require a longer timeframe or additional stimuli. These findings highlight the potential of B cells as biomarkers for disease activity and therapeutic response in psoriasis. The observed cytokine imbalance suggests that targeting B cell-mediated inflammation could be a novel therapeutic avenue. Further research is needed to assess long-term Breg dynamics and their role in maintaining immune homeostasis in psoriasis. This study reinforces the importance of both effector and regulatory B cells in psoriasis and suggests that monitoring their balance may improve disease characterization and treatment strategies.