Mesenchymal stromal cells attenuate multiple sclerosis via IDO-dependent increasing the suppressive proportion of CD5+ IL-10+ B cells

Am J Transl Res. 2019 Sep 15;11(9):5673-5688. eCollection 2019.


Multiple sclerosis (MS), one of the autoimmune and inflammatory diseases, is a major cause of neurological disability worldwide. The existing clinical treatments are not curable, and better treatments are urgently needed. Mesenchymal stromal cells (MSCs) have shown promise for treating MS, but the favorable effects and mechanism of MSC therapy on MS are still not fully understood. In this study, we analyzed the phenotypic feature of peripheral blood mononuclear cells (PBMCs) in MS patients and found that the patients exhibited an increase in the frequency of B cells, but a markedly decrease in frequency of CD5+ and IL-10+ B cells compared to healthy controls. Infusion of MSCs exhibited a significant therapeutic effect on the experimental autoimmune encephalomyelitis (EAE) mice, infiltration of mononuclear cells and demyelination of the spinal cords were both reduced in CNS of the mice, the frequency of CD5+ IL-10+ B cells in the mice was significantly increased. Additionally, when PBMCs or B cells from MS patients were co-cultured with MSCs, the frequency of CD5+ IL-10+ B cells also increased, the proliferative and immunosuppressive capacity of CD5+ B cells were significantly enhanced while the apoptosis ratio of this cellular subset significantly decreased. Moreover, those effects could be eliminated while the indoleamine 2,3-dioxygenase (IDO) inhibitor, D/L-1MT, was added to the co-cultured cells. In summary, this study suggests that MSCs can control EAE via IDO pathway to promote the proportion and function of CD5+ IL-10+ B cells, providing a promise to treat patients with MS in the clinical setting.

Keywords: Multiple sclerosis; experimental autoimmune encephalomyelitis; indoleamine 2,3-dioxygenase; mesenchymal stromal cells; regulatory B cell.