Mesenchymal Stem Cells relieved Systemic Lupus Erythematosus via CCL2 dependent macrophage polarization

Systemic lupus erythematosus (SLE) was an autoimmune disease leading to high morbidity and mortality without effective and low-side effect conventional drugs. Our previous clinical studies demonstrated umbilical cord derived mesenchymal stem cells (MSCs) were a safe and effective treatment, but its therapeutic mechanism is still unclear. In this study, we first detected the MSCs used for clinical therapy showed increased CCL2 expression than primary and aged MSCs or abnormal MSCs from SLE patients. Then, we constructed CCL2 deficient MSCs, and found the immunosuppressive activity of CCL2 deficient MSCs was impaired in the PBMC inhibitory assay in vitro. CCL2 deficient MSCs also failed to relieve SLE in MRL/lpr and pristine-induced mice. To further explore the role of CCL2 in MSCs therapy, we conducted transcriptome of CCL2 deficient MSCs and MSCs, and identified the differential expressed genes were related to chemotaxis, including monocyte chemotaxis. Subsequently, we found that MSCs restored the imbalanced macrophage polarization via CCL2 in vitro. These findings provided valuable insight for investigating the therapeutic mechanism of MSC on SLE.