Cell Reports
Volume 37, Issue 6, 9 November 2021, 109921
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Article
Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis

https://doi.org/10.1016/j.celrep.2021.109921Get rights and content
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Highlights

  • IL-33 induces fatty acid uptake programs during lung Treg cell activation

  • Acyl-CoA synthetase Acsbg1 is preferentially expressed in Treg cells

  • Acsbg1 controls mitochondrial biogenesis and cell homeostasis in Treg cells

  • Acsbg1 in lung ST2+ Treg cells is required for the resolution of lung inflammation

Summary

Regulatory T (Treg) cells are critical for immunological tolerance and immune homeostasis. Treg 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 Treg 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 Treg 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 Treg cells with oleoyl-CoA restores the phenotype of the Treg metabolic signature. Furthermore, this pathway in ST2+ effector Treg cells enhances immunosuppressive capacity in airway inflammation. Thus, Acsbg1 serves as a metabolic checkpoint governing Treg cell homeostasis and the resolution of lung inflammation.

Keywords

Treg cells
fatty acid metabolism
mitochondrial fitness
Acsbg1
airway inflammation
pathogenic Th2 cells
IL-33
IL-5

Data and code availability

  • The RNA seq data have been deposited in the Gene Expression Omnibus at NCBI (https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/geo/) under accession number GSE183667.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

8

These authors contributed equally

9

Lead contact