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

Avneesh K. Singh, Jun Qi Yang, Vrajesh V. Parekh, Jie Wei, Chyung Ru Wang, Sebastian Joyce, Ram R. Singh, Luc Van Kaer

Research output: Contribution to journalArticlepeer-review

Abstract

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 α-galactosylceramide (α-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 α-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 α-GalCer suppresses or promotes pristane-induced lupus-like autoimmunity in mice, in a strain-dependent manner.

Original languageEnglish (US)
Pages (from-to)1143-1154
Number of pages12
JournalEuropean Journal of Immunology
Volume35
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • CD1d
  • Glycolipids
  • Immunotherapy
  • NKT cells
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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