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| Status |
Public on Jul 04, 2024 |
| Title |
ACLY and ACSS2 link nutrient-dependent chromatin accessibility to regulation of CD8 T cell effector responses |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that CD8 T cell responses to infection depend on acetyl-CoA derived from citrate via the enzyme Acly (ATP citrate lyase). However, ablation of Acly triggers an alternative, acetate-dependent pathway for acetyl-CoA production mediated by Acss2 (acyl-CoA synthetase short chain family member 2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and chromatin accessibility at effector gene loci. When Acly is functional, Acss2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, deletion of Acly renders CD8 T cells dependent on acetate (via Acss2) to maintain acetyl-CoA production and effector function. Thus, together Acly and Acss2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.
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| Overall design |
C57BL/6 mice (3 biological replicates) were infected with LCMV-Armstrong. At 8 dpi, mice were sacrificed, and single cell suspensions generated
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| Contributor(s) |
Irem K, Watson M, Brandon O, Shixin M, Benjamin J, Lisa D, Susan K, Dominic R, Russell J |
| Citation missing |
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| Submission date |
May 14, 2024 |
| Last update date |
Jul 04, 2024 |
| Contact name |
Brandon Oswald |
| E-mail(s) |
Brandon.Oswald@vai.org
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| Phone |
6168343380
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| Organization name |
Van Andel Institute
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| Department |
Metabolism
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| Lab |
Russell Jones
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| Street address |
333 Bostwick Ave NE
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| City |
Grand Rapids |
| State/province |
MI |
| ZIP/Postal code |
49503 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA1111363 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267377_RAW.tar |
94.0 Mb |
(http)(custom) |
TAR (of RDS) |
SRA Run Selector |
| Raw data are available in SRA |
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