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

Abstract

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 in the development of new strategies to treat autoimmune disease. Here, a translational method for bioengineering programmed death-ligand 1 (PD-L1)- and cluster of differentiation 86 (CD86)-functionalized mouse Schwann cells (SCs) to prevent and ameliorate multiple sclerosis (MS) in established mouse models of chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE) is described. It is shown that the intravenous (i.v.) administration of immune checkpoint ligand functionalized mouse SCs modifies the course of disease and ameliorates EAE. Further, it is found that such bioengineered mouse SCs inhibit the differentiation of myelin-specific helper T cells into pathogenic T helper type-1 (T_h 1) and type-17 (T_h 17) cells, promote the development of tolerogenic myelin-specific regulatory T (T_reg ) cells, and resolve inflammatory central nervous system microenvironments without inducing systemic immunosuppression.

Keywords: Schwann cells; bioorthogonal click chemistry; experimental autoimmune encephalomyelitis; immune checkpoint; metabolic glycoengineering.