IL-1β enhances mesenchymal stem cells to induce CD8 + IL-10 + T cell differentiation in patients with rheumatoid arthritis / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To investigate the role of IL-1β in regulating human placenta-derived mesenchymal stem cells (hPMSCs) to induce the differentiation of activated peripheral blood mononuclear cells (PBMCs) into CD8 + IL-10 + T cell subset in patients with rheumatoid arthritis (RA). Methods:Serum IL-1β levels in RA patients were detected by CBA kit. hPMSCs were isolated from healthy subjects by enzyme digestion. PBMCs that were isolated from RA patients and healthy subjects by Ficoll density gradient centrifugation were activated with PHA and CD3/CD28 monoclonal antibody (McAb) and then co-cultured with hPMSCs. Flow cytometry (FCM) was used to analyze the ability of hPMSCs to induce the differentiation of activated PBMCs into CD8 + IL-10 + T cell subset with the presence of programmed death ligand 1 (PD-L1) and/or PD-L2 McAb and IL-1β. Expression of PD-L1 and PD-L2 on hPMSCs under IL-1β stimulation was analyzed by RT-PCR and FCM. Results:Serum IL-1β levels were significantly higher in RA patients than in healthy subjects. After the activation by PHA and CD3/CD28 McAb, the proportion of CD8 + IL-10 + T cells in PBMCs of RA patients was significantly lower than that of healthy subjects. Moreover, the proportion of CD8 + IL-10 + T cells significantly increased after co-cultured with hPMSCs. The ability of IL-1β-treated hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells was significantly enhanced compared to untreated hPMSCs. IL-1β could up-regulate the expression of PD-L1 and PD-L2 on hPMSCs. Blocking the expression of PD-L1 and/or PD-L2 on hPMSCs significantly reduced the ability of hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells. Conclusions:IL-1β enhanced the capacity of hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells in RA patients by up-regulating the expression of PD-L1 and PD-L2.