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Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function

MPS-Authors

Field,  Cameron
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Baixauli Celda,  Francesc
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons204373

Puleston,  Daniel
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kyle,  Ryan
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201436

Alana,  Cameron
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201442

Sanin,  Pena David Estaban
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201354

Corrado,  Mauro
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks,  Joy
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons204377

Grzes,  Katarzyna
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce,  Edward J.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Erika L.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Fulltext (public)

Field et al..pdf
(Publisher version), 5MB

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Citation

Field, C., Baixauli Celda, F., Puleston, D., Kyle, R., Alana, C., Sanin, P. D. E., et al. (2020). Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function. Cell Metabolism, 31, 422-437. doi:org/10.1016/j.cmet.2019.11.021.


Cite as: http://hdl.handle.net/21.11116/0000-0006-3B94-1
Abstract
Regulatory T cells (Tregs) subdue immune responses. Central to Treg activation are changes in lipid metabolism that support their survival and function. Fatty acid binding proteins (FABPs) are a family of lipid chaperones required to facilitate uptake and intracellular lipid trafficking. One family member, FABP5, is expressed in T cells, but its function remains unclear. We show that in Tregs, genetic or pharmacologic inhibition of FABP5 function causes mitochondrial changes underscored by decreased OXPHOS, impaired lipid metabolism, and loss of cristae structure. FABP5 inhibition in Tregs triggers mtDNA release and consequent cGAS-STING-dependent type I IFN signaling, which induces heightened production of the regulatory cytokine IL-10 and promotes Treg suppressive activity. We find evidence of this pathway, along with correlative mitochondrial changes in tumor infiltrating Tregs, which may underlie enhanced immunosuppression in the tumor microenvironment. Together, our data reveal that FABP5 is a gatekeeper of mitochondrial integrity that modulates Treg function.