Systemic immunophenotypic alterations in male mice with experimental osteoarthritis

Abstract Osteoarthritis (OA) is accompanied by an inflamed synovium containing macrophages, dendritic cells, T and B lymphocytes. Macrophages predominate and drive cytokine-mediated cartilage catabolism, while T cells and B cells, though fewer, may shape chronic adaptive responses. However, systemic immune contributions, particularly within peripheral lymphoid organs such as the spleen, remain poorly characterized. Here, we investigated whether mono-iodoacetate (MIA)-induced experimental OA in male mice is associated with splenic immunophenotypic alterations. At day 56 post-OA induction, analysis of splenocytes showed that macrophages and conventional dendritic cells (cDC1 and cDC2) displayed a significant downregulation of major histocompatibility complex class II (MHCII) expression, indicating an altered antigen-presentation-associated phenotype. OA is also associated with an increase in total DCs, primarily involving an MHCII - DC population operationally designated as “tolerogenic DCs” based on its surface phenotype. Notably, while the proportion of CD11b - tolerogenic DCs was reduced, CD11b low cells markedly expanded in OA animals. CD11b expression was upregulated on macrophages and cDC2 in MIA-induced OA mice, a change that may favor adhesive and migratory properties of myeloid cells in inflamed tissues. OA mice showed a significant reduction in the frequency of total splenic leukocytes, accompanied by a marked reduction in B-cell frequency, while total T cell frequency remained stable. However, T cell composition shifted: CD4 + T cells including activation-marker-defined and regulatory subsets decreased, whereas CD8 + T cells increased, despite reduced expression of CD25 activation markers. Together, the observed changes indicate alterations in splenic myeloid-cell phenotype, dendritic-cell subset distribution and lymphoid composition. In conclusion, our data suggest that MIA-induced chronic OA in male mice is associated with splenic immunophenotypic remodeling affecting both innate and adaptive immune compartments. These findings expand our understanding of splenic immune changes in this experimental OA model whose functional consequences remain to be accurately determined. It also provides a basis for future studies in complementary preclinical models and human disease.