Macrophages rely on extracellular serine to suppress aberrant cytokine production

Abstract A growing body of evidence indicates that cellular metabolism is involved in immune cell functions, including cytokine production. Serine is a nutritionally non-essential amino acid that can be generated by de novo synthesis and conversion from glycine. Serine contributes to various cellula...

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Autores principales:	Kento Kurita, Hiroya Ohta, Ibuki Shirakawa, Miyako Tanaka, Yasuyuki Kitaura, Yorihiro Iwasaki, Takashi Matsuzaka, Hitoshi Shimano, Seiichiro Aoe, Hiroshi Arima, Yoshihiro Ogawa, Ayaka Ito, Takayoshi Suganami
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c78ccae1fd384490939f7565d66e5db1
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spelling	oai:doaj.org-article:c78ccae1fd384490939f7565d66e5db12021-12-02T14:42:20ZMacrophages rely on extracellular serine to suppress aberrant cytokine production10.1038/s41598-021-90086-w2045-2322https://doaj.org/article/c78ccae1fd384490939f7565d66e5db12021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90086-whttps://doaj.org/toc/2045-2322Abstract A growing body of evidence indicates that cellular metabolism is involved in immune cell functions, including cytokine production. Serine is a nutritionally non-essential amino acid that can be generated by de novo synthesis and conversion from glycine. Serine contributes to various cellular responses, but the role in inflammatory responses remains poorly understood. Here, we show that macrophages rely on extracellular serine to suppress aberrant cytokine production. Depleting serine from the culture media reduced the cellular serine content in macrophages markedly, suggesting that macrophages depend largely on extracellular serine rather than cellular synthesis. Under serine deprivation, macrophages stimulated with lipopolysaccharide showed aberrant cytokine expression patterns, including a marked reduction of anti-inflammatory interleukin-10 expression and sustained expression of interleukine-6. Transcriptomic and metabolomics analyses revealed that serine deprivation causes mitochondrial dysfunction: reduction in the pyruvate content, the NADH/NAD+ ratio, the oxygen consumption rate, and the mitochondrial production of reactive oxygen species (ROS). We also found the role of mitochondrial ROS in appropriate cytokine production. Thus, our results indicate that cytokine production in macrophages is tightly regulated by the nutritional microenvironment.Kento KuritaHiroya OhtaIbuki ShirakawaMiyako TanakaYasuyuki KitauraYorihiro IwasakiTakashi MatsuzakaHitoshi ShimanoSeiichiro AoeHiroshi ArimaYoshihiro OgawaAyaka ItoTakayoshi SuganamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kento Kurita Hiroya Ohta Ibuki Shirakawa Miyako Tanaka Yasuyuki Kitaura Yorihiro Iwasaki Takashi Matsuzaka Hitoshi Shimano Seiichiro Aoe Hiroshi Arima Yoshihiro Ogawa Ayaka Ito Takayoshi Suganami Macrophages rely on extracellular serine to suppress aberrant cytokine production
description	Abstract A growing body of evidence indicates that cellular metabolism is involved in immune cell functions, including cytokine production. Serine is a nutritionally non-essential amino acid that can be generated by de novo synthesis and conversion from glycine. Serine contributes to various cellular responses, but the role in inflammatory responses remains poorly understood. Here, we show that macrophages rely on extracellular serine to suppress aberrant cytokine production. Depleting serine from the culture media reduced the cellular serine content in macrophages markedly, suggesting that macrophages depend largely on extracellular serine rather than cellular synthesis. Under serine deprivation, macrophages stimulated with lipopolysaccharide showed aberrant cytokine expression patterns, including a marked reduction of anti-inflammatory interleukin-10 expression and sustained expression of interleukine-6. Transcriptomic and metabolomics analyses revealed that serine deprivation causes mitochondrial dysfunction: reduction in the pyruvate content, the NADH/NAD+ ratio, the oxygen consumption rate, and the mitochondrial production of reactive oxygen species (ROS). We also found the role of mitochondrial ROS in appropriate cytokine production. Thus, our results indicate that cytokine production in macrophages is tightly regulated by the nutritional microenvironment.
format	article
author	Kento Kurita Hiroya Ohta Ibuki Shirakawa Miyako Tanaka Yasuyuki Kitaura Yorihiro Iwasaki Takashi Matsuzaka Hitoshi Shimano Seiichiro Aoe Hiroshi Arima Yoshihiro Ogawa Ayaka Ito Takayoshi Suganami
author_facet	Kento Kurita Hiroya Ohta Ibuki Shirakawa Miyako Tanaka Yasuyuki Kitaura Yorihiro Iwasaki Takashi Matsuzaka Hitoshi Shimano Seiichiro Aoe Hiroshi Arima Yoshihiro Ogawa Ayaka Ito Takayoshi Suganami
author_sort	Kento Kurita
title	Macrophages rely on extracellular serine to suppress aberrant cytokine production
title_short	Macrophages rely on extracellular serine to suppress aberrant cytokine production
title_full	Macrophages rely on extracellular serine to suppress aberrant cytokine production
title_fullStr	Macrophages rely on extracellular serine to suppress aberrant cytokine production
title_full_unstemmed	Macrophages rely on extracellular serine to suppress aberrant cytokine production
title_sort	macrophages rely on extracellular serine to suppress aberrant cytokine production
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c78ccae1fd384490939f7565d66e5db1
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Macrophages rely on extracellular serine to suppress aberrant cytokine production

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