SCD2-mediated monounsaturated fatty acid metabolism regulates cGAS-STING-dependent type I IFN responses in CD4+ T cells

• Published in: Communications biology Vol. 4; no. 1; pp. 820 - 14
• Main Authors: Kanno, Toshio, Nakajima, Takahiro, Yokoyama, Satoru, Asou, Hikari K., Sasamoto, Shigemi, Kamii, Yasuhiro, Hayashizaki, Koji, Ouchi, Yasuo, Onodera, Taishi, Takahashi, Yoshimasa, Ikeda, Kazutaka, Hasegawa, Yoshinori, Kinjo, Yuki, Ohara, Osamu, Nakayama, Toshinori, Endo, Yusuke
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/2; 13/21; 13/31; 13/95; 14; 631/250/127/1212; 631/250/1619/554/1898/1272; 631/250/2499; 631/326/596/2553; 64/60; Biology; Biomedical and Life Sciences; CD4 antigen; Clonal deletion; CRISPR; Fatty acids; Genomes; Interferon; Life Sciences; Lipid metabolism; Lipids; Lymphocytes; Lymphocytes T; Metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02310-y

Host lipid metabolism and viral responses are intimately connected. However, the process by which the acquired immune systems adapts lipid metabolism to meet demands, and whether or not the metabolic rewiring confers a selective advantage to host immunity, remains unclear. Here we show that viral infection attenuates the expression of genes related to lipid metabolism in murine CD4 + T cells, which in turn increases the expression of antiviral genes. Inhibition of the fatty acid synthesis pathway substantially increases the basal expression of antiviral genes via the spontaneous production of type I interferon (IFN). Using a combination of CRISPR/Cas9-mediated genome editing technology and a global lipidomics analysis, we found that the decrease in monounsaturated fatty acid caused by genetic deletion of Scd2 in mice was crucial for the induction of an antiviral response through activation of the cGAS-STING pathway. These findings demonstrate the important relationship between fatty acid biosynthesis and type I IFN responses that enhances the antiviral response. Kanno et al. demonstrate that decreased monounsaturated fatty acid in CD4 + T cells following Scd2 deletion boosts the induction of the antiviral response via activation of the cGAS-STING pathway in mice. This study highlights the important interaction between fatty acid metabolism and the acquired immune response.