MSCs relieve SLE by modulation of Th17 cells through MMPs–CCL2–CCR2–IL‐17 pathway

Abstract

Abstract Objective To explore the modulation of mesenchymal stem cells (MSCs) on T helper 17 (Th17) cells in systemic lupus erythematosus (SLE) and underlying mechanism. Methods The concentration of matrix metalloproteinases (MMPs), CC chemokine ligand‐2 (CCL2), and interleukin‐17 (IL‐17) in the serum of SLE patients and mice were detected by enzyme‐linked immunosorbent assay. The expression of CCR2 and IL‐17 of T lymphocytes were determined by flow cytometry. The effects of MSCs on Th17 cells were analyzed in lupus mice and coculture system in vitro. Results The levels of MMPs, CCL2, IL‐17, CCR2, and percentages of Th17 cells were significantly increased in SLE patients. These molecules and numbers of Th17 cells were downregulated by umbilical cord‐derived MSCs (UC‐MSCs) which relieve SLE disease. CCL2 neutralizing antibody blocked the effects of MSCs on Th17 cells. MMPs reversed the function of CCL2. Conclusion The beneficial effects of MSCs on SLE patients rely on secreting MMPs, which reverse the activity of CCL2 to inhibit Th17 cells, suggesting the crucial MSCs–MMP–CCL2–CCR2–Th17–IL‐17 pathway in SLE.

Keywords

• CC chemokine ligand‐2
• mesenchymal stem cells
• systemic lupus erythematosus
• T helper 17 cells