CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes
Guomin Ren1,2, Nedaa Al-Jezani1, Pamela Railton3
1McCaig Institute for Bone & Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Iscience
|January 25, 2021
Summary
The chemokine CCL22 influences fibroblast-like synoviocytes (FLS) in osteoarthritis (OA) by altering cytokine expression and promoting inflammation. This suggests a novel pathway contributing to OA pathogenesis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Synovitis is prevalent in osteoarthritis (OA) and linked to pain and disease progression.
- Previous research showed C-C motif chemokine 22 (CCL22) induces chondrocyte apoptosis in vitro.
- The impact of CCL22 on synovial tissue, specifically fibroblast-like synoviocytes (FLS), was previously unknown.
Purpose of the Study:
- To investigate the effects of CCL22 on FLS.
- To determine the role of CCL22 in the synovium of OA patients.
Main Methods:
- FLS were treated with CCL22.
- Gene expression of IL-4, IL-10, and S100A12 was analyzed.
- CCR3 knockdown was performed to assess its role.
- CCL22 and CCR3 expression in FLS was evaluated.
Main Results:
- CCL22 treatment suppressed IL-4 and IL-10 expression while promoting S100A12 expression in FLS.
- FLS response to CCL22 correlated with synovial fluid CCL22 levels, not disease state.
- CCL22-induced S100A12 expression in FLS was partially dependent on CCR3.
- CCL22 and S100A12 were upregulated in CCR3-positive FLS treated with CCL22.
Conclusions:
- CCL22 modulates FLS function, impacting cytokine profiles and promoting S100A12 expression.
- A potential feedforward inflammatory mechanism involving CCL22 and CCR3 in FLS was identified.
- This pathway may represent a novel therapeutic target for osteoarthritis synovitis.
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