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

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.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-3B94-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-616A-6
Genre: Journal Article

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 Creators:
Field, Cameron1, Author
Baixauli Celda, Francesc1, Author              
Puleston, Daniel1, Author              
Kyle, Ryan1, Author
Alana, Cameron1, Author              
Sanin, Pena David Estaban1, Author              
Hippen, Keli L.2, Author
Loschi, Michael2, Author
Thangavelu, Govindarajan2, Author
Corrado, Mauro1, Author              
Edwards-Hicks, Joy1, Author
Grzes, Katarzyna1, Author              
Pearce, Edward J.1, Author              
Blazar, Bruce R.2, Author
Pearce, Erika L.1, Author              
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              
2External Organizations, ou_persistent22              

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 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.

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Language(s): eng - English
 Dates: 2020-02-04
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: org/10.1016/j.cmet.2019.11.021
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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 31 Sequence Number: - Start / End Page: 422 - 437 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928