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Series GSE126245 Query DataSets for GSE126245
Status Public on Dec 26, 2019
Title Mitochondrial integrity regulated by FABP5 is a cell-intrinsic checkpoint for Treg suppressive function
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Regulatory 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.
 
Overall design RNA-seq was performed on in vitro differentiated T regulatory cells, isolated from the spleen, exposed to the FABP5 inhibitor BMS309403.
 
Contributor(s) Field CS, Biaxauli Celda F, Kyle RL, M. Cameron A, Sanin DE, Hippen KL, Loschi M, Puleston DJ, Corrado M, Edwards-Hicks J, Grzes KM, Pearce EJ, Blazar BR, Pearce EL
Citation(s) 31883840
Submission date Feb 07, 2019
Last update date Feb 18, 2020
Contact name Immunometabolism Department
E-mail(s) jcurti29@jhmi.edu
Organization name Johns Hopkins University
Department Immunometabolism
Street address 1650 Orleans Street
City Baltimore
State/province Maryland
ZIP/Postal code 21287
Country USA
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (8)
GSM3594180 Treg_1
GSM3594181 Treg_2
GSM3594182 Treg_3
Relations
BioProject PRJNA521378
SRA SRP184528

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Supplementary file Size Download File type/resource
GSE126245_RAW.tar 1.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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