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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Field CS,Baixauli F,Kyle RL,Puleston DJ,Cameron AM,Sanin DE,Hippen KL,Loschi M,Thangavelu G,Corrado M,Edwards-Hicks J,Grzes KM,Pearce EJ,Blazar BR,Pearce ELdoi
10.1016/j.cmet.2019.11.021subject
Has Abstractpub_date
2020-02-04 00:00:00pages
422-437.e5issue
2eissn
1550-4131issn
1932-7420pii
S1550-4131(19)30665-5journal_volume
31pub_type
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