Background/Purpose: Psoriatic arthritis (PsA) patients often experience joint damage mediated by osteoclasts (OC). Although PsA pathogenesis is poorly understood, the production of the cytokines IL-17, IL 23, and TNF are implicated in disease initiation and progression. TNF and IL-17 induce the expression of CX3CR1 and the CX3CR1-Fractalkine (FKN) axis promotes inflammation and bone damage in rheumatoid arthritis (RA). In addition, a tissue-resident OC that expresses CX3CR1 was identified in murine arthritis and RA synovial tissue¹. Dendritic Cell-Surface Transmembrane Protein (DC-STAMP) is expressed on OC precursors (OCP). We found that DC-STAMP^-/- mouse fibroblasts exposed to TNF do not secrete FKN and that DC-STAMP^-/- x TNFTg arthritic mice show impaired migration of CX3CR1⁺ monocytes to joints. The purpose of this study is to identify whether DC-STAMP and CX3CR1 are co-expressed on OCP in the blood and synovial tissue of PsA patients.

Methods:

We collected blood from 23 psoriatic (Ps) and 10 PsA patients to measure serum IL-17 and TNF by multiplex assay. We assessed the frequency of CD14⁺CX3CR1⁺DCSTAMP⁺ monocytes in the blood of Ps and PsA patients and controls. We used immunofluorescence to enumerate TNF and IL-17-producing cells in biopsies of non-lesional (NL) and lesional (L) skin of Ps and PsA patients, and qPCR to calculate fold changes in TNF and IL-17 mRNA expression in skin biopsies (L, NL). We enumerated DC-STAMP⁺CX3CR1⁺ monocyte subsets in 3 synovial and 5 PsA L skin biopsies.

Results: We found low serum TNF levels (Ps, 4.6 ± 1.05 vs PsA, 13.98 ± 6.8, p=0.04), high IL-17 mRNA expression (Ps, 40-fold ± 7.6 vs PsA, 4.6-fold, p = 0.04) and an increased number of IL-17⁺ cells in L skin of Ps patients (Ps, 31.5 ± 3.3 vs PsA, 7.0 ± 2.6, p = 0.0001). In contrast, PsA patients had higher systemic levels of TNF, lower IL-17 mRNA expression, and poor infiltration of IL-17⁺ cells in L skin. Interestingly, we visualized higher numbers of TNF-expressing cells in PsA synovial tissue than skin. Flow cytometry analysis showed an increased frequency of CD45⁺CD14⁺DC-STAMP⁺CX3CR1⁺ circulating monocytes in PsA (2.3%), compared to Ps (0.6%) and controls (0.001%). Intriguingly, DC-STAMP⁺CX3CR1⁺CD14⁺ and DC-STAMP⁺CX3CR1⁺ CD14^– monocytes were present only in synovial tissue, while a unique subset of CX3CR1^–DC-STAMP⁺CD14⁺ cells was present in PsA but not psoriasis skin biopsies.

Conclusion: These findings highlight the divergence of TNF and IL-17 expression in the serum and skin of psoriasis and PsA patients. The co-expression of CX3CR1 and DC-STAMP present only in synovial cells supports the presence of a tissue-resident OC that arises from precursors in the skin and blood.

¹Hasegawa T. Nat Immuno. 2019;20:1631

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/co-expression-of-dc-stamp-and-cx3cr1-biomarkers-for-tissue-resident-osteoclasts-in-psoriatic-arthritis/