Genetically Engineered Exosomes as a Potential Regulator of Th1 Cells Response in Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis is a long-lasting inflammatory disease that usually involves joints, but it can also affect other organs, including the skin and lungs. In this case, it is important to maintain a balance between beneficial pro-inflammatory activity and harmful overactivation of the T helper cells (Th). We strive to investigate in this study the possibilities for the effect of mesenchymal stem cells (MSCs)-derived exosomes containing miR-146a/miR-155 on the lymphocyte population and function. Methods: Exosomes were isolated from overexpressed miR-146a/miR-155 MSCs for the purpose of this analysis. Splenocytes were isolated from collagen-induced arthritis (CIA) and control mice. It was important to consider the expressions of certain predominant autoimmune-response genes, including T-bet and interferon-γ (IFNγ), by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. It turned out to be a significant consideration with p < 0.05. Results: The results are expressed in percentages with respect to miR-146a/AntimiR-155 transduced MSC-derived exosomes treatment, which significantly decreased the mRNA expression level of IFNγ in healthy mice (p < 0.05). miR-146a transduced MSC-derived exosomes treatment significantly reduced the mRNA expression level of IFNγ in CIA mice (p < 0.05). It should be noted that the secretion of the pro-inflammatory factor IFNγ in CIA mice was inhibited in almost all groups (p < 0.05). Conclusion: Many research groups have mainly focused on strategies for reducing pro-inflammatory cytokines. This approach was recently suggested and investigated in our research team and suggested that manipulation of MSCs-derived exosomes could minimize pro-inflammatory cytokine production to strike a balance among Th subsets. These approaches tend to appear to achieve better results in the regulation of the immune system by the use of engineered exosomes derived from MSCs. By providing accurate information the reasonably practicable use of exosomes for cell-free therapy can be established.