title: Ly108 expression distinguishes subsets of invariant NKT cells that help autoantibody production and secrete IL-21 from those that secrete IL-17 in lupus prone NZB/W mice.
abstract: 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 NKT 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 NKT cells expressed the Ly108(lo)CD4(-)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. α-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.
authors: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
authors: Xiaobin
authors: X
authors: Tang
authors: Department of Chemistry, Stanford University, Stanford, CA, USA.
authors: Bo
authors: B
authors: Zhang
authors: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
authors: Justin A
authors: JA
authors: Jarrell
authors: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
authors: Jordan V
authors: JV
authors: Price
authors: Department of Chemistry, Stanford University, Stanford, CA, USA.
authors: Hongjie
authors: H
authors: Dai
authors: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
authors: Paul J
authors: PJ
authors: Utz
authors: Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: sstrober@stanford.edu.
authors: Samuel
authors: S
authors: Strober
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology; D000098546:Interleukin-21; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D000974:Antibodies, Antinuclear; D018941:Antigens, CD19; D000950:Antigens, Ly; D005699:Galactosylceramides; D007074:Immunoglobulin G; D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21; C493154:alpha-galactosylceramide; C000604063:Slamf6 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family
keywords: Autoantibodies; IL-17; IL-21; Natural killer T cells; Systemic lupus erythematosus