Galectin-3 Deficiency Reduces the Severity of Experimental Autoimmune Encephalomyelitis

Abstract

Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectin family and plays an important role in inflammation. However, the precise role of Gal-3 in autoimmune diseases remains obscure. We have investigated the functional role of Gal-3 in experimental autoimmune encephalomyelitis (EAE) following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Gal-3 deficient (Gal-3-/-) mice developed significantly milder EAE and markedly reduced leukocyte infiltration in the CNS compared with similarly treated wild-type (WT) mice. Gal-3-/- mice also contained fewer monocytes and macrophages but more apoptotic cells in the CNS than did WT mice. Following Ag stimulation in vitro, lymph node cells from the immunized Gal-3-/- mice produced less IL-17 and IFN-gamma than did those of the WT mice. In contrast, Gal-3-/- mice produced more serum IL-10, IL-5, and IL-13 and contained higher frequency of Foxp3+ regulatory T cells in the CNS than did the WT mice. Furthermore, bone marrow-derived dendritic cells from Gal-3-/- mice produced more IL-10 in response to LPS or bacterial lipoprotein than did WT marrow-derived dendritic cells. Moreover, Gal-3-/- dendritic cells induced Ag-specific T cells to produce more IL-10, IL-5, and IL-12, but less IL-17, than did WT dendritic cells. Taken together, our data demonstrate that Gal-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10 production.

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…73 Gal-3 has a known role in atopic dermatitis and asthma by promoting an anti-inflammatory Th2 response, while it diminishes the Th2 response in Paracoccidioides infection by negatively regulating IL-10 production. 74 Gal-3 affects Th1, 75 Th2, 74 and Th17 responses, 76 depending on the infecting pathogen. Presumably, this is dependent on the type of receptors involved and their interaction with the stimulant.…”

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

“…Interestingly, gal3 also suppresses the regulatory T cell response through downregulating IL-10 release by DCs and, thus, induces Th1/Th17 responses to aggravate experimental autoimmune encephalomyelitis (EAE) (11). Gal3 2/2 mice were demonstrated to have reduced inflammation and neutrophil recruitment in infections by Streptococcus pneumoniae and T. gondii (6), atherosclerosis (12), EAE (11), and dextran sulfate sodium-induced colitis (13). However, little is known about the relationship between gal3 and production of IL-23/IL-17A-axis cytokines.…”

The Two Faces of Galectin-3: Roles in Various Pathological Conditions

“…Some evidence suggested that Galectin-3 is associated with a decrease in regulatory T (Treg) cell frequency and thus influences the course of experimental autoimmune encephalomyelitis and Leishmania major infection (98,99). These results raise the question of whether Galectin-3 deficiency also impaired the number of Treg cells in an experimental model of B16-F1 murine melanoma.…”