Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice

Abstract The nuclear receptors liver X receptor α (LXRα) and LXRβ are lipid sensors that regulate lipid metabolism and immunity. Natural killer T (NKT) cells, a T cell subset expressing surface markers of both natural killer cells and T lymphocytes and involved in antitumor immunity, are another abu...

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Autores principales:	Kaori Endo-Umeda, Hiroyuki Nakashima, Shigeyuki Uno, Shota Toyoshima, Naoki Umeda, Shihoko Komine-Aizawa, Shuhji Seki, Makoto Makishima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ee757d79ffd4b2fb91c334e28f90050
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spelling	oai:doaj.org-article:0ee757d79ffd4b2fb91c334e28f900502021-11-21T12:20:04ZLiver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice10.1038/s41598-021-02062-z2045-2322https://doaj.org/article/0ee757d79ffd4b2fb91c334e28f900502021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02062-zhttps://doaj.org/toc/2045-2322Abstract The nuclear receptors liver X receptor α (LXRα) and LXRβ are lipid sensors that regulate lipid metabolism and immunity. Natural killer T (NKT) cells, a T cell subset expressing surface markers of both natural killer cells and T lymphocytes and involved in antitumor immunity, are another abundant immune cell type in the liver. The potential function of the metabolic regulators LXRα/β in hepatic NKT cells remains unknown. In this study, we examined the role of LXRα and LXRβ in NKT cells using mice deficient for LXRα and/or LXRβ, and found that hepatic invariant NKT (iNKT) cells are drastically decreased in LXRα/β-KO mice. Cytokine production stimulated by the iNKT cell activator α-galactosylceramide was impaired in LXRα/β-KO hepatic mononuclear cells and in LXRα/β-KO mice. iNKT cell-mediated antitumor effect was also disturbed in LXRα/β-KO mice. LXRα/β-KO mice transplanted with wild-type bone marrow showed decreased iNKT cells in the liver and spleen. The thymus of LXRα/β-KO mice showed a decreased population of iNKT cells. In conclusion, LXRα and LXRβ are essential for NKT cell-mediated immunity, such as cytokine production and hepatic antitumor activity, and are involved in NKT cell development in immune tissues, such as the thymus.Kaori Endo-UmedaHiroyuki NakashimaShigeyuki UnoShota ToyoshimaNaoki UmedaShihoko Komine-AizawaShuhji SekiMakoto MakishimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kaori Endo-Umeda Hiroyuki Nakashima Shigeyuki Uno Shota Toyoshima Naoki Umeda Shihoko Komine-Aizawa Shuhji Seki Makoto Makishima Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
description	Abstract The nuclear receptors liver X receptor α (LXRα) and LXRβ are lipid sensors that regulate lipid metabolism and immunity. Natural killer T (NKT) cells, a T cell subset expressing surface markers of both natural killer cells and T lymphocytes and involved in antitumor immunity, are another abundant immune cell type in the liver. The potential function of the metabolic regulators LXRα/β in hepatic NKT cells remains unknown. In this study, we examined the role of LXRα and LXRβ in NKT cells using mice deficient for LXRα and/or LXRβ, and found that hepatic invariant NKT (iNKT) cells are drastically decreased in LXRα/β-KO mice. Cytokine production stimulated by the iNKT cell activator α-galactosylceramide was impaired in LXRα/β-KO hepatic mononuclear cells and in LXRα/β-KO mice. iNKT cell-mediated antitumor effect was also disturbed in LXRα/β-KO mice. LXRα/β-KO mice transplanted with wild-type bone marrow showed decreased iNKT cells in the liver and spleen. The thymus of LXRα/β-KO mice showed a decreased population of iNKT cells. In conclusion, LXRα and LXRβ are essential for NKT cell-mediated immunity, such as cytokine production and hepatic antitumor activity, and are involved in NKT cell development in immune tissues, such as the thymus.
format	article
author	Kaori Endo-Umeda Hiroyuki Nakashima Shigeyuki Uno Shota Toyoshima Naoki Umeda Shihoko Komine-Aizawa Shuhji Seki Makoto Makishima
author_facet	Kaori Endo-Umeda Hiroyuki Nakashima Shigeyuki Uno Shota Toyoshima Naoki Umeda Shihoko Komine-Aizawa Shuhji Seki Makoto Makishima
author_sort	Kaori Endo-Umeda
title	Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
title_short	Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
title_full	Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
title_fullStr	Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
title_full_unstemmed	Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice
title_sort	liver x receptors regulate natural killer t cell population and antitumor activity in the liver of mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0ee757d79ffd4b2fb91c334e28f90050
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Liver X receptors regulate natural killer T cell population and antitumor activity in the liver of mice

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