The natural killer T cell ligand alpha-galactosylceramide prevents or promotes pristane-induced lupus in mice.
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.
Singh
Avneesh K
AK
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Yang
Jun-Qi
JQ
Parekh
Vrajesh V
VV
Wei
Jie
J
Wang
Chyung-Ru
CR
Joyce
Sebastian
S
Singh
Ram R
RR
Van Kaer
Luc
L
D000818:Animals; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D013729:Terpenes / Q000494:pharmacology
D005699:Galactosylceramides; D007166:Immunosuppressive Agents; D013729:Terpenes; C493154:alpha-galactosylceramide; C009042:pristane