Galectin-1 is essential for the induction of MOG35-55 -based intravenous tolerance in experimental autoimmune encephalomyelitis.

MARI ER,; RASOULI J, ; CIRIC B,; MOORE JN, ; CONEJO-GARCIA JR, ; RAJASAGI N,; ZHANG GX, ; RABINOVICH GA, ; ROSTAMI A.

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2016

0014-2980

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 Treg cells 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 Treg cells in the CNS and periphery, and reduced IL-27, IL-10 and TGF-β1 expression in DCs in the periphery. 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, Treg cells and downregulation of pro-inflammatory responses. This article is protected by copyright. All rights reserved.