Background Interleukin-7 (IL-7), a member of the common gamma-chain cytokine family, plays a crucial role in T cell development, which induces T cell survival, proliferation, differentiation in mature naive and memory T cells. IL-7 is expressed by stromal cells, epithelial cells, and fibroblasts. IL-7 is highly expressed in synovial tissue (ST) of patients with rheumatoid arthritis (RA) and its expression level correlates with the disease activity. Although IL-7Rα is mainly expressed in T cells, IL-7 receptor α (IL-7Rα) is able to be expressed in CD19-positive B cells and monocytes of synovial fluid mononuclear cells (SFMC) in RA patients. IL-7 promotes the secretion of osteoclastogenic factors, such as M-CSF and RANKL, in T cells, and eventually induces osteoclastogenesis. In contrast, It has been shown that IL-7α-deficient mice promote osteoclastogenesis and IL-7 treatment inhibits the osteoclastogenesis in vitro. Thus, the role of IL-7 involved in osteoclastogenesis is still unclear.
Objectives In order to resolve this discrepancy, we investigated the effect of IL-7 on the differentiation of monocytes into osteoclasts.
Methods First, we examined the expression level of IL-7Rα in several subsets from PBMC and SFMC of RA patients as well as healthy subjects. Second, we determined the direct role of IL-7 in osteoclast differentiation of monocytes expressing IL-7Rα in vitro.
Results As results, we found that IL-7Rα was highly expressed in monocytes from RA SFMC compared to health PBMC, and its expression was confined to specific monocyte-subsets, intermediate monocyte (CD14+CD16+) and inflammatory monocyte (CD14-CD16++). Furthermore, IL-7 induced osteoclastogenesis from RA monocytes in the presence or absence of M-CSF and RANKL, and also promoted the osteoclastogenesis in earlier than done by M-CSF and RANKL.
Conclusions These finding suggest that IL-7 may directly affect monocyte differentiation in osteoclast cells in inflammatory condition, such as synovial fluid of RA, and blocking IL-7 or IL-7Rα as therapy may give a new pathway to treatment of bone erosion in patient with RA.
Disclosure of Interest : None declared
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