A myeloid population potentially corresponding to myeloid monocytic suppressor cells (MoMDSCs) is increased in the blood of Rheumatoid Arthritis patients and associated with osteoclastogenesis

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Abstract The development of erosive arthritis and joint damage are common and severe complications of rheumatoid arthritis (RA). Erosions are caused by excessive activity of osteoclasts (OCs), the only known bone resorbing cells. OCs are myeloid lineage cells and can be generated in vitro from CD14+ circulating myeloid cells, using RANKL and M-CSF. To characterize circulating myeloid lineage cells in RA, we performed mass cytometry (CyTOF) analysis of blood from 11 RA patients and 10 age and gender-matched healthy controls. Using CITRUS analysis, we found a myeloid cell cluster that is significantly elevated in RA patients compared to healthy subjects. The phenotype of this cluster is CD11b+, CD14+, CD16−, HLA-DR-/lo, CCR2hi, RANKhi, and phosphorylated (p)STAT3hi. The surface phenotype of this cluster is associated with monocytic myeloid derived suppressor cells (MoMDSCs). Analysis by conventional flow of a separate group of 14 RA patients showed that frequency of these myeloid cells correlates with number of blood osteoclasts precursors (OCP) based on the in vitro assay. Baseline level of pSrc and pJNK in these cells also correlated with OCP numbers. Both of these molecules are involved in downstream signaling cascades involved in osteoclastogenesis and osteoclast survival. We also found that intermediate (CD14++CD16+) monocytes are elevated in RA, as previously described, but these cells did not show a positive correlation with OCP numbers. These results indicate that a group of myeloid cells, potentially corresponding to MoMDSCs, are elevated in the blood of RA patients. Their phenotype (high RANK, phosphorylated Src, phosphorylated JNK) and frequency indicate that they may be involved in osteoclastogenesis, as described in mouse models.