Artikel
IL-34 in the pathogenesis of human rheumatoid and lupus arthritis
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Veröffentlicht: | 8. Oktober 2019 |
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Gliederung
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Background: While myeloid cells are abundant in lupus arthritis (LA) and rheumatoid arthritis (RA), based on clinical presentation LA and RA are considered distinct diseases. As imaging improves, it becomes increasingly clear that LA in SLE patients also leads to destruction of the joint and connective tissue. Although inflammatory arthritis is common in patients with lupus, the pivotal mechanisms leading to a possible destructive inflammation have not been investigated.
Results: We report the novel findings that IL-34 and CSF-1 are upregulated in the serum and urine in LA and RA patients but only IL-34, not CSF-1, tracks with clinical activity in LA and RA patients. To investigate possible IL-34 dependent mechanisms we found that IL-34 is more robustly expressed in the synovial tissue, cells and fluid compared to CSF-1 in both LA and RA. Moreover, IL-34 promotes fibroblast-like synoviocyte (FLS) proliferation via signaling through both IL-34 receptors, cFMS (shared with CSF-1) and protein-tyrosine phosphatase (PTPRZ); This Il-34 mediated proliferation of FLS is far more robustly than that promoted by CSF-1. An addition, IL-34 released from stimulated FLS increases chemokines expression and thereby recruits neutrophils and monocytes (Mo) into the synovium; and induces neutrophils and Mo to express reactive oxygen species (ROS), known to perpetuate intra-synovial inflammation.
Conclusion: IL-34-dependent mechanisms are pivotal and similar in mediating LA and RA. Moreover, tracking serum IL-34 might be a reliable biomarker for managing the individualized treatment of patients with LA.