Temporal dynamics of systemic immune cell networks in C57BL/6 mice with collagen-induced arthritis

Collagen-induced arthritis (CIA) model in C57BL/6 (H-2^b background) mice provides a valuable model for studying the pathogenesis of rheumatoid arthritis (RA). However, the immune mechanism underlying this model remains unclear. This study aims to comprehensively understand the dynamic multi-dimensional characteristics of CIA, especially the temporal changes in immune cell subsets, providing a basis for future research on immune-targeted therapy for RA. The CIA course was divided into onset, peak, and chronic stages based on arthritis scores. Joint pathology was assessed by histology; immune cell subsets in the spleen and lymph nodes were profiled by flow cytometry; and serum cytokines were measured by ELISA. The results revealed distinct stage-specific immune alterations during CIA progression. M1 polarization occurred at the onset stage. DCs were markedly activated at the peak stage, accompanied by elevated frequencies of Th1, Th17, and Tfh cells, while the Breg cell proportions declined. Moreover, DC activation and abundant Th1 and Tfh cells persisted into the chronic stage. Neutrophils remained elevated throughout disease progression to sustain inflammatory responses. Furthermore, upregulated TNF-α and decreased TGF-β1 represented the core cytokine alterations driving CIA pathogenesis. Collectively, this study provided in-depth insights into dynamic immune shifts during CIA progression and offered valuable clues for developing novel RA immunotherapies.