Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue T reg cell homeostasis

Regulatory T (T ) cells are critical for immunological tolerance and immune homeostasis. T cells strongly rely on mitochondrial metabolism and show a lower level of glycolysis. However, little is known about the role of lipid metabolism in the regulation of T cell homeostasis. Some members of the AC...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2021-11, Vol.37 (6), p.109921
Main Authors: Kanno, Toshio, Nakajima, Takahiro, Kawashima, Yusuke, Yokoyama, Satoru, Asou, Hikari K, Sasamoto, Shigemi, Hayashizaki, Koji, Kinjo, Yuki, Ohara, Osamu, Nakayama, Toshinori, Endo, Yusuke
Format: Article
Language:English
Subjects:
Animals
Coenzyme A Ligases - genetics
Coenzyme A Ligases - metabolism
Disease Models, Animal
Energy Metabolism
Fatty Acids - metabolism
Gene Expression Regulation, Enzymologic
Homeostasis
Interleukin-33
Lung - enzymology
Lung - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria - enzymology
Mitochondria - genetics
Mitochondria - immunology
Organelle Biogenesis
Pneumonia - enzymology
Pneumonia - genetics
Pneumonia - immunology
Signal Transduction
T-Lymphocytes, Regulatory - enzymology
T-Lymphocytes, Regulatory - immunology
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Summary:Regulatory T (T ) cells are critical for immunological tolerance and immune homeostasis. T cells strongly rely on mitochondrial metabolism and show a lower level of glycolysis. However, little is known about the role of lipid metabolism in the regulation of T cell homeostasis. Some members of the ACSL family of acyl-coenzyme A (CoA) synthases are expressed in T cells, but their function remains unclear. A combination of RNA-sequencing and proteome analyses shows that Acsbg1, a member of ACSL, is selectively expressed in T cells. We show that the genetic deletion of Acsbg1 not only causes mitochondrial dysfunction, but it also dampens other metabolic pathways. The extrinsic supplementation of Acsbg1-deficient T cells with oleoyl-CoA restores the phenotype of the T metabolic signature. Furthermore, this pathway in ST2 effector T cells enhances immunosuppressive capacity in airway inflammation. Thus, Acsbg1 serves as a metabolic checkpoint governing T cell homeostasis and the resolution of lung inflammation.
ISSN:2211-1247
DOI:10.1016/j.celrep.2021.109921