Galectin‐1 is essential for the induction of MOG_35–55‐based intravenous tolerance in experimental autoimmune encephalomyelitis

Abstract

In experimental autoimmune encephalomyelitis (EAE), intravenous (i.v.) injection of the antigen, myelin oligodendrocyte glycoprotein-derived peptide, MOG35-55, suppresses disease development, a phenomenon called i.v. tolerance. Galectin-1, an endogenous glycan-binding protein, is upregulated during autoimmune neuroinflammation and plays immunoregulatory roles by inducing tolerogenic dendritic cells (DCs) and IL-10-producing regulatory type 1 T (Tr1) cells. To examine the role of galectin-1 in i.v. tolerance, we administered MOG35-55-i.v. to wild-type (WT) and galectin-1-deficient (Lgals1−/−) mice with ongoing EAE. MOG35-55 suppressed disease in the WT, but not in the Lgals1−/− mice. The numbers of Tr1 cells and Tregs were increased in the CNS and periphery of tolerized WT mice. In contrast, Lgals1−/− MOG-i.v. mice had reduced numbers of Tr1 cells and Tregs in the CNS and periphery, and reduced IL-27, IL-10 and TGF-β1 expression. DCs derived from i.v. tolerized WT mice suppressed disease when adoptively transferred into mice with ongoing EAE, whereas DCs from Lgals1−/− MOG-i.v. mice were not suppressive. These findings demonstrate that galectin-1 is required for i.v. tolerance induction, likely via induction of tolerogenic DCs leading to enhanced development of Tr1 cells, Tregs and downregulation of pro-inflammatory responses.

Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance

“…contain galectin-1 (68), a lectin that mediates activation-induced T cell apoptosis (69) and inhibits autoimmune arthritis and experimental autoimmune encephalomyelitis development (70,71), they could also regulate local responses in the testis microenvironment, particularly near the location where premeiotic germ cells normally transit the Sertoli cell barrier.…”

The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis

“…This is also shown by the inhibitory effect on T-cell proliferation upon binding of galectin-1 to NP-1, a glycoprotein counterreceptor [213,271]. Consistently, induction of EAE in Lgals1 −/− mice increases the severity of symptoms via a T helper cell response mechanism and a concomitant increase in classically activated microglia and axonal damage [270]. Moreover, adoptive transfer of galectin-1-secreting astrocytes or galectin-1-treated microglia augmented EAE symptoms via a mechanism that involves deactivation of pro-inflammatory microglia [212].…”

“…Mediates alternative activation by PI3K activation upon binding to CD98 [279] edges, and in subsets of CD4 + Th1 cells and microglia before and at the onset of EAE symptoms, while its expression remains increased in astrocytes at the chronic stage [212]. Intravenously administration of galectin-1, either before or at EAE onset, results in a reduced severity of symptoms [268], mainly by inducing tolerogenic dendritic cells, selective elimination of pro-inflammatory Th1 and Th17 cells and enhanced development of Tr1 and regulatory T cells [269,270]. This is also shown by the inhibitory effect on T-cell proliferation upon binding of galectin-1 to NP-1, a glycoprotein counterreceptor [213,271].…”

Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis

“…DCs exert opposing functions in EAE by either inducing or suppressing disease . TolDCs possess features of lower level co‐stimulatory signals and pro‐inflammatory cytokines, but higher expression of co‐inhibitory molecules and anti‐inflammatory cytokines, which are helpful for restoring immune tolerance in autoimmune diseases .…”