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
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Publicado: Nature Portfolio 2021
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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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