Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis.
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.
Jiang
Hui-Rong
HR
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
Al Rasebi
Zakeya
Z
Mensah-Brown
Eric
E
Shahin
Allen
A
Xu
Damo
D
Goodyear
Carl S
CS
Fukada
Sandra Y
SY
Liu
Fu-Tong
FT
Liew
Foo Y
FY
Lukic
Miodrag L
ML
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D037502:Galectin 3 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000276:immunology
D037502:Galectin 3; D006023:Glycoproteins; D006131:Growth Inhibitors; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10