Stearoyl-CoA Desaturase-Mediated Monounsaturated Fatty Acid Availability Supports Humoral Immunity

Xian Zhou; Xingxing Zhu; Chaofan Li; Yanfeng Li; Zhenqing Ye; Virginia Smith Shapiro; John A. Copland; Taro Hitosugi; David A. Bernlohr; Jie Sun; Hu Zeng

doi:10.1016/j.celrep.2020.108601

Stearoyl-CoA Desaturase-Mediated Monounsaturated Fatty Acid Availability Supports Humoral Immunity

Xian Zhou, Xingxing Zhu, Chaofan Li, Yanfeng Li, Zhenqing Ye, Virginia Smith Shapiro, John A. Copland, Taro Hitosugi, David A. Bernlohr, Jie Sun, Hu Zeng

Metabolic and Systems Biology (BMBB)

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Immune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The roles of different FA species and their impacts on humoral immunity remain poorly understood. Here, we report that proliferating B cells require monounsaturated FAs (MUFAs) to maintain mitochondrial metabolism and mTOR activity and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell-extrinsic stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.

Original language	English (US)
Article number	108601
Journal	Cell reports
Volume	34
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2020.108601
State	Published - Jan 5 2021

Bibliographical note

Funding Information:
We thank Dr. Douglas Green at St. Jude Children’s Research Hospital for spleen cells from GFP-LC3 mice. We thank Dr. Michael Jensen for his expert advice on FA metabolism. This work was partly supported by National Institutes of Health (NIH) grants R01 CA225680 (to T.H.), R01 AG047156 , R01 AI112844 , and R01 AI147394 (to J.S.) and a Discovery Science Award ( 93059065 ) from the Center for Biomedical Discovery at Mayo Clinic (to H.Z.). The Mayo Clinic Metabolomics Core is supported by NIH grant U24DK100469 .

Funding Information:
We thank Dr. Douglas Green at St. Jude Children's Research Hospital for spleen cells from GFP-LC3 mice. We thank Dr. Michael Jensen for his expert advice on FA metabolism. This work was partly supported by National Institutes of Health (NIH) grants R01 CA225680 (to T.H.), R01 AG047156, R01 AI112844, and R01 AI147394 (to J.S.) and a Discovery Science Award (93059065) from the Center for Biomedical Discovery at Mayo Clinic (to H.Z.). The Mayo Clinic Metabolomics Core is supported by NIH grant U24DK100469. X. Zhou designed and performed the cellular, molecular, and animal experiments and wrote the manuscript. X. Zhu and Y.L. carried out animal experiments and microscopy data analysis. C.L. performed influenza infection and heatmap graph. Z.Y. performed RNA-seq data analysis. T.H. performed OA oxidation assays. J.A.C. provided SSI-4 and SSI-4 chow. V.S.S. T.H. D.A.B. and J.S. provided research materials and assisted data interpretation. H.Z. designed experiments, wrote the manuscript, and supervised the study. H.Z. and J.A.C. have a pending patent application regarding use of the SCD inhibitor SSI-4.

Publisher Copyright:
© 2020 The Authors

Keywords

B cell
autophagy
humoral immunity
mTOR
monounsaturated fatty acid
stearoyl-CoA desaturase

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

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10.1016/j.celrep.2020.108601

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title = "Stearoyl-CoA Desaturase-Mediated Monounsaturated Fatty Acid Availability Supports Humoral Immunity",

abstract = "Immune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The roles of different FA species and their impacts on humoral immunity remain poorly understood. Here, we report that proliferating B cells require monounsaturated FAs (MUFAs) to maintain mitochondrial metabolism and mTOR activity and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell-extrinsic stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.",

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author = "Xian Zhou and Xingxing Zhu and Chaofan Li and Yanfeng Li and Zhenqing Ye and Shapiro, {Virginia Smith} and Copland, {John A.} and Taro Hitosugi and Bernlohr, {David A.} and Jie Sun and Hu Zeng",

note = "Funding Information: We thank Dr. Douglas Green at St. Jude Children{\textquoteright}s Research Hospital for spleen cells from GFP-LC3 mice. We thank Dr. Michael Jensen for his expert advice on FA metabolism. This work was partly supported by National Institutes of Health (NIH) grants R01 CA225680 (to T.H.), R01 AG047156 , R01 AI112844 , and R01 AI147394 (to J.S.) and a Discovery Science Award ( 93059065 ) from the Center for Biomedical Discovery at Mayo Clinic (to H.Z.). The Mayo Clinic Metabolomics Core is supported by NIH grant U24DK100469 . Funding Information: We thank Dr. Douglas Green at St. Jude Children's Research Hospital for spleen cells from GFP-LC3 mice. We thank Dr. Michael Jensen for his expert advice on FA metabolism. This work was partly supported by National Institutes of Health (NIH) grants R01 CA225680 (to T.H.), R01 AG047156, R01 AI112844, and R01 AI147394 (to J.S.) and a Discovery Science Award (93059065) from the Center for Biomedical Discovery at Mayo Clinic (to H.Z.). The Mayo Clinic Metabolomics Core is supported by NIH grant U24DK100469. X. Zhou designed and performed the cellular, molecular, and animal experiments and wrote the manuscript. X. Zhu and Y.L. carried out animal experiments and microscopy data analysis. C.L. performed influenza infection and heatmap graph. Z.Y. performed RNA-seq data analysis. T.H. performed OA oxidation assays. J.A.C. provided SSI-4 and SSI-4 chow. V.S.S. T.H. D.A.B. and J.S. provided research materials and assisted data interpretation. H.Z. designed experiments, wrote the manuscript, and supervised the study. H.Z. and J.A.C. have a pending patent application regarding use of the SCD inhibitor SSI-4. Publisher Copyright: {\textcopyright} 2020 The Authors",

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AU - Zhu, Xingxing

AU - Li, Chaofan

AU - Li, Yanfeng

AU - Ye, Zhenqing

AU - Shapiro, Virginia Smith

AU - Copland, John A.

AU - Hitosugi, Taro

AU - Bernlohr, David A.

AU - Sun, Jie

AU - Zeng, Hu

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N2 - Immune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The roles of different FA species and their impacts on humoral immunity remain poorly understood. Here, we report that proliferating B cells require monounsaturated FAs (MUFAs) to maintain mitochondrial metabolism and mTOR activity and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell-extrinsic stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.

AB - Immune cells can metabolize glucose, amino acids, and fatty acids (FAs) to generate energy. The roles of different FA species and their impacts on humoral immunity remain poorly understood. Here, we report that proliferating B cells require monounsaturated FAs (MUFAs) to maintain mitochondrial metabolism and mTOR activity and to prevent excessive autophagy and endoplasmic reticulum (ER) stress. Furthermore, B cell-extrinsic stearoyl-CoA desaturase (SCD) activity generates MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.

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ER -

Stearoyl-CoA Desaturase-Mediated Monounsaturated Fatty Acid Availability Supports Humoral Immunity

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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