title: Galectin-1-induced down-regulation of T lymphocyte activation protects (NZB x NZW) F1 mice from lupus-like disease.
abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a hyperactive immune system, including activation of autoreactive T and B cells. These studies demonstrate that administration of recombinant galectin-1, a β-galactose binding protein, to SLE-prone (NZB × NZW) F1 mice reduced lymphocyte activation, inhibited serum anti-double-stranded DNA(dsDNA) IgG antibody production, decreased the incidence of proteinuria, and increased survival rate. In addition, recombinant galectin-1'-treated mice had a higher frequency of Foxp3 expression, which suggested an increase in the percentage of peripheral regulatory T cells. Consistent with the finding that there were fewer activated T lymphocytes, ex vivo T cells from mice treated with recombinant galectin-1 exhibited less proliferation in response to TCR stimulation. Furthermore, these cells were less efficient at lipid raft clustering in response to TCR/CD28 engagement, consistent with published reports that galectin-1 can reorganize the synaptic contact to interfere with TCR signaling and activation to prevent T cell activation. Aged galectin-1-deficient mice had higher serum levels of antibodies against dsDNA, elucidating a role for endogenous galectin-1 in decreasing susceptibility to autoimmunity. Together, the findings highlight galectin-1 as a novel potential therapeutic immune modulator for treatment of lupus-like disease.
authors.affiliation: University of California, Los Angeles, CA, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: La Cava
authors.forename: C C
authors.initials: CC
authors.lastname: Motran
authors.forename: B H
authors.initials: BH
authors.lastname: Hahn
authors.forename: M C
authors.initials: MC
authors.lastname: Miceli
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004247:DNA / Q000276:immunology; D015536:Down-Regulation; D004353:Drug Evaluation, Preclinical; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D037483:Galectin 1 / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D021962:Membrane Microdomains / Q000187:drug effects; D051379:Mice; D057507:Mice, 129 Strain; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D001323:Autoantibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037483:Galectin 1; D007074:Immunoglobulin G; C445499:LGALS1 protein, human; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D004247:DNA