Programmed Cell Death Ligand 1-Transfected Mouse Bone Marrow Mesenchymal Stem Cells as Targeted Therapy for Rheumatoid Arthritis

Abstract

Programmed cell death 1 ligand (PD-L1) and its receptor (PD-1) are key molecules for immunoregulation and immunotherapy. PD-L1 binding PD-1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD-L1 by constructing a recombinant of PD-L1-lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen-induced arthritis (CIA) in DBA/1j mice. In addition, PD-L1-transfected MBMMSCs (PD-L1-MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD-L1-MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD-L1-MBMMSC-targeted therapy.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells

“…MSCs with high PD-L1 expression have better therapeutic effect on RA, and antagonism of PD-L1 will reduce the efficacy. 132 , 133 BM-MSCs attenuate bleomycin-induced pulmonary fibrosis and improve lung function through the PD-1/PD-L1 pathway, by reducing T cell infiltration and inflammatory factor release. 134 In addition, PD-L1 expressed on MSCs is also associated with other chronic diseases.…”

The Role of Mesenchymal Stromal Cells in the Treatment of Rheumatoid Arthritis

“…Mouse BM-MSCs with overexpressed programmed cell death 1 ligand (PD-L1) reduced the percentage of Th1 and Th17 but enhanced that of Tregs. PD-L1-transfected mouse BM-MSCs had lower concentrations of pro-inflammatory cytokines, including IL-1β, IL-6, IL-17, IFN-γ, and TNF-α, while levels of anti-inflammatory IL-10 were increased [ 98 ]. BM-MSCs reduce the number of CD4+ and CD8+ T cells, thereby reducing the levels of IL-2, IL-6, IL-9, IL-17, IFN-γ, and TNF-α.…”

PD-L1’s Role in Preventing Alloreactive T Cell Responses Following Hematopoietic and Organ Transplant

“…Moreover, there was limited cartilage damage, synovial hyperplasia, inflammatory cell infiltration, and bone erosion in the mice treated with the PD-L1 overexpression vector. These transplanted stem cells decreased the DCs found in mouse joints and increased the Tregs in the tissue, promoting a tolerant and non-inflammatory environment [ 121 ].…”