期刊
CYTOKINE & GROWTH FACTOR REVIEWS
卷 55, 期 -, 页码 86-93出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2020.05.007
关键词
CCL21; CCR7; Rheumatoid arthritis; Joint inflammation; Osteoclastogenesis; Angiogenesis
资金
- National Psoriasis Foundation (NPF), Department of Veteran's Affairs MERIT Award [1I01BX002286]
- National Institutes of Health [AR056099, AR065778]
- Pfizer Investigator-Initiated Research (IIR) Program
- Chicago Biomedical Consortium (CBC) Accelerator Award
Innate and adaptive immunity regulate the inflammatory and erosive phenotypes observed in rheumatoid arthritis (RA) patients. Hence, identifying novel pathways that participate in different stages of RA pathology will provide valuable insights concerning the mechanistic behavior of different joint leukocytes and the strategy to restrain their activity. Recent findings have revealed that CCL21 poses as a risk factor for RA and expression of its receptor, CCR7, on circulating monocytes is representative of the patient's disease activity score. Expression of CCR7 was found to be the hallmark of RA synovial fluid (SF) M1 macrophages (M Phi s) and its levels were potentiated in response to M1 mediating factors and curtailed by M2 mediators in naive M Phi s. Intriguingly, although both CCR7 ligands, CCL19 and CCL21, are elevated in RA specimens, only CCL21 was predominately responsible for CCR7's pathological manifestation of RA. Unique subset of M Phi s differentiated in response to CCL21 stimulation, exhibited upregulation in Th17-polarizing monokines. Moreover, CCL21-activated monokines were capable of differentiating naive T cells into joint Th17 cells, which also partook in RA osteoclastogenesis. Finally, to conserve chronic inflammation, SF CCL21 amplified RA neovascularization directly and indirectly by promoting RA FLS and M Phi s to secrete proangiogenic factors, VEGF and IL-17. This review aims to shed light on the broad pathogenic impact of CCL21, linking immunostimulatory M Phi s with Th17 cells, while concurrently advancing RA bone destruction and neovascularization.
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