Background/Purpose:

Focal erosions in inflammatory arthritis are mediated by bone marrow (BM) derived osteoclasts (OC) that enter the joint as OC precursors (OCP) from peripheral blood. We have previously shown that DC-STAMP (Dendritic Cell-Specific Transmembrane protein), a 7-pass transmembrane protein essential for cell-to-cell fusion during OC differentiation, is a valid biomarker of circulating OCPs. In bone marrow (BM), naive lymphocytes encounter self-antigens to establish immune tolerance and interact with OC and osteoblast progenitors. Herein, we dissected T cell, B cell and monocyte populations, compared the percentage of these cell populations between patients and healthy individuals, examined the potential of these cells in lineage differentiation, and searched for cell subsets uniquely present in BM.

Methods:

BM and PBMC collected from 2 psoriatic arthritis (PsA), 2 psoriasis (Ps) patients and 4 healthy controls (HC) were processed and purified by Ficoll gradient, stained by antibodies, and analyzed by flow cytometry. To assess differentiation potential, cells were cultured in dendritic cell (DC)-promoting, Th17-promoting, and OC-promoting media. Phagocytic activity was assessed by FITC-dextran beads.

Results:

The OCP frequency of BM and PBMC was 3,423±306 and 1,340±120 per 10e6 monocytes, respectively. Monocytes in BM differentiated into functional DC with phagocytic activity as evidenced by the intake of FITC-dextran beads. T cells in BM differentiated into Th17-like T cells (IL17A+IL23R+DC-STAMP+CCR6+) after in vitro  culture in Th-17-promoting media. Patients with both Ps and PsA had a higher percentage of DC-STAMP⁺IL17A⁺ cells in the BM (patients:11.4%, HC:2.6%) and a higher percentage of IgD+CD27+CXCR3+ memory B cells in both BM and PBMC than HC (HC/patients= 3/60 for BM and 24/69 for PBMC). Intriguingly, a novel DC-STAMP-expressing monocyte subset (DC-STAMP⁺CD14⁺CD11b⁺CD16-CD34^–CD45 (intermediate)), composing of approximately 18% of rosette monocytes, was only present in BM but absent in PBMC.

Conclusion:

In this study, we (1) identified a novel subset of DC-STAMP⁺ monocytes which is uniquely present in BM but absent in PBMC; (2) showed that BM has 3-fold more OCPs than peripheral blood; (3) found that monocytes and T cells in BM can differentiate into OC/DC and Th17 cells with full effector functions; (4) identified variations in T, B, monocyte populations between PBMC and BM; (5) found that patients with Ps and PsA had a higher % of 1A2+IL17A+CD3+ T cells and IgD+CD27+CXCR3+ B cells in BM than controls.

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« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/expansion-of-dc-stamp-il-17-cells-in-bone-marrow-from-psoriasis-and-psoriatic-arthritis-patients/