Journal
JOURNAL OF AUTOIMMUNITY
Volume 50, Issue -, Pages 87-98Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2014.01.002
Keywords
Natural killer T cells; Systemic lupus erythematosus; Autoantibodies; IL-17; IL-21
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Funding
- NIH research grant [RO1 DK082537]
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Lupus is a systemic autoimmune disease characterized by anti-nuclear antibodies in humans and genetically susceptible NZB/W mice that can cause immune complex glomerulonephritis. T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secreting helper factors such as IL-21 that promote production of IgG autoantibodies. In the current study, we determined whether purified NICT cells or far more numerous conventional non-NKT cells in the spleen of NZB/W female mice secrete IL-17 and/or IL-21 after TCR activation in vitro, and provide help for spontaneous IgG autoantibody production by purified splenic CD19(+) B cells. Whereas invariant NKT cells secreted large amounts of IL-17 and IL-21, and helped B cells, non-NKT cells did not. The subset of IL-17 secreting NZB/W NICT cells expressed the Ly108(hi)CD(+)NK1.1(-)phenotype, whereas the IL-21 secreting subset expressed the Ly108(hi)CD4(+)NK1.1(-) phenotype and helped B cells secrete a variety of IgG anti-nuclear antibodies. alpha-galactocylceramide enhanced the helper activity of NZB/W and B6.Sle1b NKT cells for IgG autoantibody secretion by syngeneic B cells. In conclusion, different subsets of iNKT cells from mice with genetic susceptibility to lupus can contribute to pathogenesis by secreting pro-inflammatory cytokines and helping autoantibody production. (c) 2014 Elsevier Ltd. All rights reserved.
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