Macrophages rely on extracellular serine to suppress aberrant cytokine production

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

研究成果: ジャーナルへの寄稿学術誌査読

6 被引用数 (Scopus)


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.

ジャーナルScientific reports
出版ステータス出版済み - 12月 2021

!!!All Science Journal Classification (ASJC) codes

  • 一般


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