Immune Checkpoint Ligand-Bioengineered Schwann Cells as Antigen-Specific Therapy for Experimental Autoimmune Encephalomyelitis.

Failure to establish immune tolerance leads to the development of autoimmune disease. The ability to regulate autoreactive T cells without inducing systemic immunosuppression represents a major challenge to develop new strategies to treat autoimmune disease. Here, we describe a translational method for bioengineering programmed death-ligand 1 and cluster of differentiation 86-functionalized mouse Schwann cells to prevent and ameliorate multiple sclerosis in established mouse models of chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). We show here that the intravenous administration of immune checkpoint ligand-functionalized mouse Schwann cells modifies the course of disease and ameliorates EAE. Further, we found that such bioengineered mouse Schwann cells inhibit the differentiation of myelin-specific helper T cells into pathogenic T helper type 1 and type 17 cells, promote the development of tolerogenic myelin-specific regulatory T cells and resolve inflammatory CNS microenvironments without inducing systemic immunosuppression. This article is protected by copyright. All rights reserved.