Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice
Abstract Lupus nephritis is a crucial complication of systemic lupus erythematosus. In this study, we investigated the roles of mouse natural killer T (NKT) cells in lupus nephritis. From 24 weeks of age, NZB/NZW F1 mice were injected with alpha-galactosylceramide (α-GalCer) or vehicle once a week f...
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2018
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oai:doaj.org-article:ac99edb139cf49b3ad842ac3b0879ae82021-12-02T15:08:55ZRepeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice10.1038/s41598-018-26470-w2045-2322https://doaj.org/article/ac99edb139cf49b3ad842ac3b0879ae82018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-26470-whttps://doaj.org/toc/2045-2322Abstract Lupus nephritis is a crucial complication of systemic lupus erythematosus. In this study, we investigated the roles of mouse natural killer T (NKT) cells in lupus nephritis. From 24 weeks of age, NZB/NZW F1 mice were injected with alpha-galactosylceramide (α-GalCer) or vehicle once a week for four weeks. In the α-GalCer group, the levels of proteinuria and blood urea nitrogen were significantly lower than those in the vehicle group. The histological evaluation showed a decrease in glomerular immune complex deposits and an alleviation of podocyte injury. The proportion of NKT cells in the mononuclear cell (MNC) fraction in the α-GalCer group was significantly decreased in the liver, kidney, and spleen. The proliferation and cytokine production in α-GalCer-stimulated liver MNCs were markedly diminished in the α-GalCer group (anergy). The IFN-γ production in liver MNCs stimulated by concanavalin A or an anti-CD3 antibody did not differ between the two groups, whereas the IL-4 production was significantly lower in the α-GalCer group. In addition, the IgM production in CpG-oligodeoxynucleotide-stimulated spleen MNCs was significantly lower in the α-GalCer group. These results suggest that α-GalCer suppressed Th2 immune responses in NKT cells and B cell function, thereby slowing the progression of lupus nephritis.Takahiro UchidaHiroyuki NakashimaAkira YamagataSeigo ItoTakuya IshikiriyamaMasahiro NakashimaShuhji SekiHiroo KumagaiNaoki OshimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
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Medicine R Science Q Takahiro Uchida Hiroyuki Nakashima Akira Yamagata Seigo Ito Takuya Ishikiriyama Masahiro Nakashima Shuhji Seki Hiroo Kumagai Naoki Oshima Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
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Abstract Lupus nephritis is a crucial complication of systemic lupus erythematosus. In this study, we investigated the roles of mouse natural killer T (NKT) cells in lupus nephritis. From 24 weeks of age, NZB/NZW F1 mice were injected with alpha-galactosylceramide (α-GalCer) or vehicle once a week for four weeks. In the α-GalCer group, the levels of proteinuria and blood urea nitrogen were significantly lower than those in the vehicle group. The histological evaluation showed a decrease in glomerular immune complex deposits and an alleviation of podocyte injury. The proportion of NKT cells in the mononuclear cell (MNC) fraction in the α-GalCer group was significantly decreased in the liver, kidney, and spleen. The proliferation and cytokine production in α-GalCer-stimulated liver MNCs were markedly diminished in the α-GalCer group (anergy). The IFN-γ production in liver MNCs stimulated by concanavalin A or an anti-CD3 antibody did not differ between the two groups, whereas the IL-4 production was significantly lower in the α-GalCer group. In addition, the IgM production in CpG-oligodeoxynucleotide-stimulated spleen MNCs was significantly lower in the α-GalCer group. These results suggest that α-GalCer suppressed Th2 immune responses in NKT cells and B cell function, thereby slowing the progression of lupus nephritis. |
format |
article |
author |
Takahiro Uchida Hiroyuki Nakashima Akira Yamagata Seigo Ito Takuya Ishikiriyama Masahiro Nakashima Shuhji Seki Hiroo Kumagai Naoki Oshima |
author_facet |
Takahiro Uchida Hiroyuki Nakashima Akira Yamagata Seigo Ito Takuya Ishikiriyama Masahiro Nakashima Shuhji Seki Hiroo Kumagai Naoki Oshima |
author_sort |
Takahiro Uchida |
title |
Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
title_short |
Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
title_full |
Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
title_fullStr |
Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
title_full_unstemmed |
Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
title_sort |
repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/ac99edb139cf49b3ad842ac3b0879ae8 |
work_keys_str_mv |
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1718387958380232704 |