Galectin-1 plays an essential role in intravenous tolerance in experimental autoimmune encephalomyelitis (BA4P.139)

Abstract

Abstract Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases of the central nervous system (CNS). EAE can be induced by immunizing mice with myelin oligodendrocyte glycoprotein-derived peptide, MOG35-55, in adjuvant. It has been previously demonstrated that intravenous (i.v.) injection of MOG35-55 post immunization induction suppresses disease development, a phenomenon called i.v. tolerance. The glycan-binding protein galectin-1, produced primarily by regulatory T cells plays an immunoregulatory role in EAE by inducing tolerogenic DCs and IL-10-producing regulatory type 1 T cells (Tr1). To examine the role of galectin-1 in i.v. tolerance, we administered MOG35-55 peptide i.v. to wild-type (WT) and galectin-1-/- (Gal1-/-) mice with ongoing EAE. MOG35-55 rapidly suppressed disease in the WT, but not in the Gal1-/- mice. Expression of pro-inflammatory cytokines IFN-gamma and IL-17A were reduced in the CNS and periphery of tolerized WT mice, while the number of Tr1 cells increased in the periphery. In contrast, i.v. MOG35-55 significantly increased IFN-gamma and IL-17A in the CNS and periphery of Gal1-/-mice and these mice had markedly fewer Tr1 cells in the periphery. Our data suggest that galectin-1 mediated i.v. tolerance induction is dependent on the downregulation of Th1 and Th17 pro-inflammatory responses, and enhanced development of Tr1 cells.