Beta-galactosylceramide alters invariant natural killer T cell function and is effective treatment for lupus.
NZB/W female mice spontaneously develop systemic lupus, an autoantibody mediated disease associated with immune complex glomerulonephritis. Natural killer (NK) T cells augment anti-dsDNA antibody secretion by NZB/W B cells in vitro, and blocking NKT cell activation in vivo with anti-CD1 mAb ameliorates lupus disease activity. In the current study, we show that beta-galactosylceramide reduces the in vivo induction of serum IFN-gamma and/or IL-4 by the potent NKT cell agonist alpha-galactosylceramide and reduces NKT cell helper activity for IgG secretion. Treatment of NZB/W mice with the beta-galactosylceramide ameliorated lupus disease activity as judged by improvement in proteinuria, renal histopathology, IgG anti-dsDNA antibody formation, and survival. In conclusion, beta-galactosylceramide, a glycolipid that reduces the cytokine secretion induced by a potent NKT cell agonist ameliorates lupus in NZB/W mice.
Morshed
Sufi R
SR
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Takahashi
Tsuyoshi
T
Savage
Paul B
PB
Kambham
Neeraja
N
Strober
Samuel
S
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002518:Ceramides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D009005:Monosaccharides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011507:Proteinuria / Q000473:pathology / Q000652:urine; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis
D000974:Antibodies, Antinuclear; D055610:Antigens, CD1d; D002518:Ceramides; D009005:Monosaccharides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C511581:beta-galactosyl ceramide; D015847:Interleukin-4; D007371:Interferon-gamma