GSE126245 Mitochondrial integrity regulated by FABP5 is a cell-intrinsic checkpoint for Treg suppressive function

Contributors : Cameron S Field ; Fran Biaxauli Celda ; Ryan L Kyle ; Alanna M. Cameron ; David E Sanin ; Keli L Hippen ; Michael Loschi ; Daniel J Puleston ; Mauro Corrado ; Joy Edwards-Hicks ; Katarzyna M Grzes ; Edward J Pearce ; Bruce R Blazar ; Erika L PearceSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusRegulatory T cells (Tregs) negatively regulate immune-mediated inflammation that is essential for preventing autoimmunity, but which can be detrimental in cancer. Central to Treg activation are changes in lipid metabolism to support their survival and function. Fatty acid binding proteins (FABPs) are a family of lipid chaperones required to facilitate the uptake and trafficking of intracellular lipids. One family member, FABP5, is expressed in certain T cell subsets, but its function remains elusive. We show here that in Tregs, FABP5 inhibition causes mitochondrial defects, underscored by decreased OXPHOS, lipid elongation and desaturation, and loss of cristae structure, which augment their suppressive function. Mitochondrial dysfunction after FABP5 inhibition results in mtDNA release and consequent cGAS/STING-dependent type I IFN signaling, which induces increased production of the regulatory cytokine IL-10, promoting Treg cell suppressive activity. Together these data reveal that FABP5 acts as a gatekeeper of mitochondrial health to control Treg cell function.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research