Role of the CCL28-CCR10 pathway in monocyte migration in rheumatoid arthritis.
- Author:
Fang CHENG
1
;
Shao Ying YANG
2
;
Xing Xing FANG
3
;
Xuan WANG
3
;
Fu Tao ZHAO
1
Author Information
1. Department of Rheumatology and Immunology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China.
2. Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
3. Department of Rheumatology and Immunology, Tongji Hospital, Tongji University, Shanghai 200065, China.
- Publication Type:Journal Article
- Keywords:
Chemokine CCL28;
Chemokine receptor CCR10;
Monocytes;
Rheumatoid arthritis
- MeSH:
Humans;
Monocytes/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Endothelial Cells/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Arthritis, Rheumatoid;
Synovial Membrane;
Chemokines, CC/metabolism*;
Synovial Fluid;
Osteoarthritis;
Receptors, CCR10/metabolism*
- From:
Journal of Peking University(Health Sciences)
2022;54(6):1074-1078
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To examine the expression of chemokine receptor CCR10 on monocytes/macrophages in the joints of patients with rheumatoid arthritis (RA), and to investigate the role of chemokine CCL28 and its receptor CCR10 in the migration of RA monocytes and its mechanism.
METHODS:The expression of CCR10 in synovial tissues from 8 RA patients, 4 osteoarthritis (OA) patients, and 4 normal controls was analyzed by immunohistochemistry, and cell staining was scored on a 0-5 scales. Flow cytometry was used to measure the percentage of CCR10 positive cells in CD14+ monocytes from peripheral blood of 26 RA patients and 20 healthy controls, as well as from synovial fluid of 15 RA patients. The chemotactic migration of monocytes from RA patients and healthy controls in response to CCL28 was evaluated using an in vitro Transwell system. Western blotting was conducted to assess phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways in RA monocytes upon CCL28 treatment.
RESULTS:CCR10 was predominantly expressed in RA synovial lining cells and sublining macrophages, endothelial cells, and lymphocytes. CCR10 expression was significantly increased on lining cells and sublining macrophages in RA synovial tissue compared with OA and normal synovial tissue (both P < 0.01). The patients with RA had markedly elevated expression of CCR10 on peripheral blood CD14+ monocytes compared with the healthy controls [(15.6±3.0)% vs. (7.7±3.8)%, P < 0.01]. CCR10 expression on synovial fluid monocytes from the RA patients was (32.0±15.0)%, which was significantly higher than that on RA peripheral blood monocytes (P < 0.01). In vitro, CCL28 caused significant migration of CD14+ monocytes from peripheral blood of the RA patients and the healthy controls at concentrations ranging from 10-100 μg/L (all P < 0.01). The presence of neutralizing antibody to CCR10 greatly suppressed CCL28-driven chemotaxis of RA monocytes (P < 0.01). Stimulation of RA monocytes with CCL28 induced a remarkable increase in phosphorylation of ERK and Akt (both P < 0.05). ERK inhibitor (U0126) and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) strongly reduced the migration of RA monocytes in response to CCL28 (both P < 0.01).
CONCLUSION:RA patients had increased CCR10 expression on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages. CCL28 ligation to CCR10 promoted RA monocyte migration through activation of the ERK and PI3K/Akt signaling pathways. The CCL28-CCR10 pathway could participate in monocyte recruitment into RA joints, thereby contributing to synovial inflammation and bone destruction.
