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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Autores principales: Takahiro Uchida, Hiroyuki Nakashima, Akira Yamagata, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/ac99edb139cf49b3ad842ac3b0879ae8
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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AT seigoito repeatedadministrationofalphagalactosylceramideamelioratesexperimentallupusnephritisinmice
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