Fig 2: CD5L production identifies efferocytosis-prone CD14⁺ monocytes in RA patients. CD5L protein levels were measured in supernatants from CD14⁺ cell cultures of 35 RA patients. Cultures with CD5L concentrations > 0.6 pg/mL (twice the detection limit) were classified as CD5Lhi (n = 10), whereas the remaining samples were classified as CD5Llow (n = 25). A CD5L, IL-10, and PD-L1 protein levels in culture supernatants; white blood cell (WBC) and platelet counts; and serum IFN-γ levels in CD5Lhi and CD5Llow patients. B Normalized gene expression in CD14⁺ cells measured by RNA-seq. Differential expression analysis was performed using DESeq2, and nominal p-values are indicated

Fig 3: CD5L induces an anti-inflammatory phenotype in human monocytes. A Representative flow cytometry histograms showing CD11b and CD29 expression in human CD11b⁺CD14⁺CD4⁻ cells stimulated as indicated. Mean fluorescence intensity (MFI) of CD11b and CD29 is shown for n = 8 donors. p-values were calculated using the paired Wilcoxon test. B CD16 expression on intermediate (IM; CD14⁺CD16⁺) and non-classical (NCM; CD14lowCD16⁺) monocyte subsets. C Protein levels of IL-10, PD-L1, IFN-γ, and GAS6 measured in culture supernatants. * p < 0.05; ** p < 0.01; *** p < 0.001

Fig 4: Low CD5L expression in synovial macrophages associates with joint damage in RA. A CD5L protein levels in serum from RA patients and healthy controls (left), and paired serum and synovial fluid samples from RA patients (right). B Spearman correlation coefficients (ρ) between serum CD5L levels or vdH–Sharp score and serological markers. C Correlation analyses of serum CD5L levels versus vdH–Sharp score in 80 RA patients (left), and the CD5L-dependent gene signature in non-classical monocytes versus vdH–Sharp score (right). D Frequency of CD5L⁺ cells within the synovial myeloid cell cluster. E UMAP visualization of CD5L-dependent signature expression in synovial myeloid cells assessed by single-cell RNA-seq. F Gene expression changes (log₂ fold change) in the CD5L-dependent osteoclastogenic signature of blood CD14⁺ cells in relation to vdH–Sharp score and serum CD5L levels. Differential expression analysis was performed using DESeq2; nominal p-values are indicated. * p < 0.05; ** p < 0.01; *** p < 0.001

Fig 5: HDAC inhibition promotes CD5L production and an anti-inflammatory phenotype in human monocytes. A Protein levels in supernatants from human blood leukocyte cultures (n = 14) stimulated as indicated. IL-10 and IFN-γ levels were normalized to mock controls. B Heat maps showing Spearman correlation coefficients (ρ) between CD5L and IL-10 concentrations in culture supernatants and the frequency of CD16⁺ cells measured by flow cytometry. C Frequencies of classical (CM; CD14⁺CD16⁻), intermediate (IM; CD14⁺CD16⁺), and non-classical (NCM; CD14.lowCD16⁺) monocyte subsets in stimulated human leukocyte cultures (n = 14). p-values were calculated using the paired Wilcoxon test. * p < 0.05; ** p < 0.01; *** p < 0.001