High Humidity Aggravates Collagen-induced Arthritis in Mice by Increasing the Expression of Splenic Myeloid-derived Suppressor Cells

Abstract Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and bone destruction, leading to severe complications. Previous research has suggested that high humidity conditions may exacerbate RA, but the underlying mechanisms remain unclear. Furthermore, there is a lack of evidence linking humidity to the worsening of RA symptoms in animal models. Methods: We utilized C57BL/6 mice to establish the CIA mouse model. The arthritis status of mice was assessed under two different humidities (50% and 80%). ELISA was used to measure the concentrations of autoantibodies and pro-inflammatory factors. Histopathological changes in spleen tissues were observed through H&E and immunohistochemistry. Mass cytometry was employed to investigate changes in cell types in the spleens of CIA mice under high humidity conditions. Additionally, we evaluated oxidative stress markers associated with MDSCs and conducted mRNA sequencing of sorted MDSCs to investigate their impact on arthritis in CIA mice. Results: Compared to normal humidity, high humidity exacerbated arthritis incidence in mice, leading to increased arthritis scores,swelling, serum autoantibodies (anti-COII and anti-CCP), and upregulation of pro-inflammatory cytokines. Significant variations were observed in the spleen index under conditions of high humidity, accompanied by noticeable inflammatory alterations. Furthermore, Elevated humidity levels induced a substantial modulation in MDSCs population in the spleen of CIA mice, along with alterations in oxidative stress markers such as heightened serum ROS levels, and increased expression of COX, SOD, and Nrf2 mRNA. Following successful sorting of MDSCs, mRNA sequencing revealed a decrease in the expression of Rap1 signaling pathway under high humidity environment, which may contribute to the increase of MDSCs cells and aggravate the progression of RA disease. Conclusion: Our comprehensive analysis demonstrates that high humidity is a negative factor in the occurrence and development of RA, potentially mediated by the influence of the Rap1 signaling pathway on MDSCs.