Considering the controversial issue of whether MSC therapy is effective in the treatment of multiple sclerosis, it is important to seek more powerful data to clarify the effect of MSCs. B7-H4 is a unique costimulatory molecule that belongs to the B7 ligand family and is broadly expressed in both lymphoid and non-lymphoid tissues. Previous studies have shown that B7-H4 is involved in regulating the progression of autoimmune diseases. However, its role in MSCs and stem cell transplantation remains unclear. In this study, we focus on C3H10 T1/2 cells, which are mouse-derived mesenchymal stem cells. And we investigated the role of B7-H4 in C3H10 T1/2 cells and explored its underlying mechanisms. As a result, downregulation of B7-H4 induced apoptosis and impaired the cell proliferation of C3H10 T1/2 cells. Further results showed that cells were arrested in the G0/G1 phase after knockdown of B7-H4. Furthermore, an EAE model was induced in female C57BL/6 mice by injecting MOG 35-55, and we investigated the effect of C3H10 T1/2 cell transplantation for the EAE model after downregulation of B7-H4 in vivo. We found that C3H10 cells can migrate to the area of spinal cord lesions, and depletion of B7-H4 attenuated the immunoregulatory effect of C3H10 T1/2 cells in vivo. Together, our findings suggest that B7-H4 is important for C3H10 cells to exert neurorestoration and therefore may be a potential molecular target for stem cell transplant strategies.
Keywords: Autoimmune diseases; B7-H4; C3H10 T1/2 cells; Stem cell transplantation.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.