Immature Exosomes Derived from MicroRNA-146a Overexpressing Dendritic Cells Act as Antigen-Specific Therapy for Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is a neurological autoimmune disease characterized by fluctuating weakness of certain voluntary muscles. Current treatments for MG are largely directed at suppressing the whole immune system by using immunosuppressants or glucocorticoids and often cause several side effects. The ideal therapeutic methods for MG should suppress aberrant immunoactivation specifically, while retaining normal function of the immune system. In this study, we first produced exosomes from microRNA-146a overexpressing dendritic cells (DCs). Then, we observed suppressive effects of those exosomes in experimental autoimmune myasthenia gravis (EAMG) mice. Results showed that exosomes from microRNA-146a overexpressing DCs expressed decreased levels of CD80 and CD86. In experimental autoimmune MG, exosomes from microRNA-146a overexpressing DCs suppressed ongoing clinical MG in mice and altered T helper cell profiles from Th1/Th17 to Th2/Treg both in serum and spleen, and the therapeutic effects of those exosomes were antigen-specific and partly dose dependent. All the findings provide experimental basis for antigen-specific therapy of MG.

Keywords: dendritic cell; exosomes; microRNA; myasthenia gravis; therapy.