Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis

H-R Jiang, Z. Al Rasebi, E. Mensah-Brown, A. Shahin, D. Xu, C.S. Goodyear, S.Y. Fukuda, F.T. Liu, Foo-Yew Liew, Miodrag L Lukic

Research output: Contribution to journalArticle

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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.
LanguageEnglish
Pages1167-1173
Number of pages7
JournalJournal of Immunology
Volume182
Issue number2
Publication statusPublished - 15 Jan 2009

Fingerprint

Galectin 3
Autoimmune Experimental Encephalomyelitis
Interleukin-10
Dendritic Cells
Interleukin-17
Interleukin-5
Bone Marrow
Galectins
Interleukin-13
Regulatory T-Lymphocytes
Interleukin-12
Autoimmune Diseases
Lipoproteins
Monocytes
Immunization
Leukocytes
Lymph Nodes
Macrophages

Keywords

  • animals
  • apoptosis
  • cells
  • cultured
  • central nervous system
  • down-regulation/immunology
  • encephalomyelitis
  • autoimmune
  • galectin 3
  • glycoproteins
  • growth inhibitors
  • interleukin-10
  • male
  • mice
  • peptide fragments

Cite this

Jiang, H-R., Al Rasebi, Z., Mensah-Brown, E., Shahin, A., Xu, D., Goodyear, C. S., ... Lukic, M. L. (2009). Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. Journal of Immunology, 182(2), 1167-1173.
Jiang, H-R ; Al Rasebi, Z. ; Mensah-Brown, E. ; Shahin, A. ; Xu, D. ; Goodyear, C.S. ; Fukuda, S.Y. ; Liu, F.T. ; Liew, Foo-Yew ; Lukic, Miodrag L. / Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. In: Journal of Immunology. 2009 ; Vol. 182, No. 2. pp. 1167-1173.
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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.",
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Jiang, H-R, Al Rasebi, Z, Mensah-Brown, E, Shahin, A, Xu, D, Goodyear, CS, Fukuda, SY, Liu, FT, Liew, F-Y & Lukic, ML 2009, 'Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis' Journal of Immunology, vol. 182, no. 2, pp. 1167-1173.

Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. / Jiang, H-R; Al Rasebi, Z.; Mensah-Brown, E.; Shahin, A.; Xu, D.; Goodyear, C.S.; Fukuda, S.Y.; Liu, F.T.; Liew, Foo-Yew; Lukic, Miodrag L.

In: Journal of Immunology, Vol. 182, No. 2, 15.01.2009, p. 1167-1173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis

AU - Jiang, H-R

AU - Al Rasebi, Z.

AU - Mensah-Brown, E.

AU - Shahin, A.

AU - Xu, D.

AU - Goodyear, C.S.

AU - Fukuda, S.Y.

AU - Liu, F.T.

AU - Liew, Foo-Yew

AU - Lukic, Miodrag L

PY - 2009/1/15

Y1 - 2009/1/15

N2 - 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.

AB - 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.

KW - animals

KW - apoptosis

KW - cells

KW - cultured

KW - central nervous system

KW - down-regulation/immunology

KW - encephalomyelitis

KW - autoimmune

KW - galectin 3

KW - glycoproteins

KW - growth inhibitors

KW - interleukin-10

KW - male

KW - mice

KW - peptide fragments

UR - http://www.ncbi.nlm.nih.gov/pubmed/19124760

UR - http://jimmunol.org/content/182/2/1167.abstract

M3 - Article

VL - 182

SP - 1167

EP - 1173

JO - Journal of Immunology

T2 - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -

Jiang H-R, Al Rasebi Z, Mensah-Brown E, Shahin A, Xu D, Goodyear CS et al. Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. Journal of Immunology. 2009 Jan 15;182(2):1167-1173.