Beneficial Effect of Tolerogenic Dendritic Cells Pulsed with MOG Autoantigen in Experimental Autoimmune Encephalomyelitis

Abstract

We found that VitD3-TolDC-MOG treatment showed a beneficial effect, not only decreasing the incidence of the disease but also reducing the severity of the clinical signs mediated by induction of regulatory T cells (Treg), as well as IL-10 production and reduction of Ag-specific lymphoproliferation. Our results support VitD3-TolDC-peptide(s) treatment as a potential strategy to restore tolerance in autoimmune diseases such as MS.

Tolerogenic Dendritic Cells Induced by BD750 Ameliorate Proinflammatory T cell Responses and Experimental Autoimmune Encephalitis in Mice

“…Given that tolDC are relatively stable in phenotype and function (13), autologous tolDC may be valuable for inducing T cell tolerance (29). Although it might be difficult for tolDC to pass the CNS (26), they did inhibit splenic Th1 and Th17 responses in EAE mice, similar to a previous report (26). In addition, although BD750 did not affect IL-10 production by LPS-stimulated DCs, BD750-DC secreted a low level of but not AKT phosphorylation, consistent with our previous findings (15).…”

“…Previous studies have shown that tolDC can inhibit autoimmune diseases, such as rheumatoid arthritis and EAE, in rodents (24,25). Indeed, pharmacological modification is a new strategy to induce tolDC (10,26). It is well known that the JAK/STAT pathway is crucial for the maturation and tolerance of DCs (16).…”

An antigen-specific semi-therapeutic treatment with local delivery of tolerogenic factors through a dual-sized microparticle system blocks experimental autoimmune encephalomyelitis

“…Results from this approach demonstrated tolerable safety profiles. Similarly, MS-specific DC-based immunotherapy has been investigated through delivery of exogenously-loaded DCs with MOG 40-55 tolerized with vitamin D 3 , and was shown to ameliorate EAE [71]. Unfortunately, adoptive DC therapy is limited by high cost, inadequate cell sources, and safety concerns [66, 72].…”

Interferon-γ and tumor necrosis factor-α promote the ability of human placenta–derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4+interleukin-10+ and CD8+interleukin-10+Treg subsets

“…Meanwhile, in in vivo studies, it was demonstrated that transplantation of hPMSCs could reduce the symptoms of many autoimmune diseases, for instance, experimental autoimmune encephalomyelitis (EAE), a common animal model of MS [11]. Moreover, Mansilla et al [12] found that induction of CD4 þ CD25 þ FOXP3 þ Treg could reduce the severity of autoimmune diseases such as EAE. The CD4 þ interleukin (IL)-10 þ T-cell subset, a new Treg subset that is involved in the negative regulation in T-cell response, was found in a murine study [13].…”