The natural killer T cell ligand alpha-galactosylceramide prevents or promotes pristane-induced lupus in mice.

Singh AK, Yang JQ, Parekh VV, Wei J, Wang CR, Joyce S, Singh RR, Van Kaer L
Eur J Immunol. 2005 35 (4): 1143-54

PMID: 15761849 · PMCID: PMC2291523 · DOI:10.1002/eji.200425861

Systemic lupus erythematosus is a systemic autoimmune disease characterized by inflammation in organs such as kidneys and presence of autoantibodies against nuclear antigens. We have previously shown that CD1d deficiency in BALB/c mice exacerbates lupus nephritis and autoantibody production induced by the hydrocarbon oil pristane. Here, we have tested the impact of activating CD1d-restricted natural killer T (NKT) cells on pristane-induced lupus-like autoimmunity in BALB/c and SJL mice. Repeated in vivo treatment of pristane-injected BALB/c mice with the NKT cell ligand alpha-galactosylceramide (alpha-GalCer) prior to the onset of florid disease suppressed proteinuria, in a manner that was dependent on CD1d and IL-4 expression. In sharp contrast, however, similar treatment of pristane-injected SJL mice with alpha-GalCer resulted in increased proteinuria. Consistent with these dichotomous effects of NKT cell activation on the development of lupus-like autoimmunity, NKT cells in BALB/c and SJL/J mice exhibited a mixed Th1/Th2 and a Th1-biased cytokine production profile, respectively. These findings demonstrate that NKT cell activation with alpha-GalCer suppresses or promotes pristane-induced lupus-like autoimmunity in mice, in a strain-dependent manner.

MeSH Terms (9)

Animals Disease Models, Animal Galactosylceramides Immunosuppressive Agents Killer Cells, Natural Lupus Erythematosus, Systemic Mice Mice, Inbred BALB C Terpenes

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