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Series GSE233901 Query DataSets for GSE233901
Status Public on Feb 28, 2024
Title Mitochondrial regulator CRIF1 deficiency induces Foxp3low inflammatory non-suppressive regulatory-T cells in tumors [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Foxp3low inflammatory non-suppressive (INS)-regulatory T cells (Tregs) were discovered recently. Unlike conventional Tregs, they produce proinflammatory-cytokines, exhibit reduced suppressiveness, and promote rather than impair anti-tumor immunity. The role of mitochondria in Foxp3low INS-Treg formation in vivo is unclear. We showed that the Foxp3low INS-Treg equivalents in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3low INS-Tregs with mitochondrial dysfunction. The -ketoglutarate-mTORC1 axis was enhanced in these cells. This promoted proinflammatory-cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased -ketoglutarate-derived 2-hydroxyglutarate downregulated Foxp3 expression by methylating the Foxp3-gene regulatory regions. Furthermore, CRIF1-deficiency-induced Foxp3low INS-Tregs suppressed tumor growth in an IFN- dependent manner. Thus, CRIF1-mediated mitochondrial homeostasis is critical for inducing Foxp3low INS-Tregs that promote anti-tumor immunity.
 
Overall design Tregs were sorted by flow cytometry, and RNA-seq and ATAC-seq was performed.
 
Contributor(s) Lee S, Kim G, Shin HM, Chung DH
Citation(s) 38536932
Submission date Jun 01, 2023
Last update date Apr 04, 2024
Contact name Sangsin Lee
E-mail(s) say891117@naver.com
Organization name Seoul National University
Street address Daehakro
City Seoul
ZIP/Postal code 03080
Country South Korea
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7438894 Control Treg unstim (rep1), RNA-seq
GSM7438895 Control Treg unstim (rep2), RNA-seq
GSM7438896 CRIF1 KO Treg unstim (rep1), RNA-seq
This SubSeries is part of SuperSeries:
GSE233903 Mitochondrial regulator CRIF1 deficiency induces Foxp3low inflammatory non-suppressive regulatory-T cells in tumors
Relations
BioProject PRJNA978546

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Supplementary file Size Download File type/resource
GSE233901_Transcript_counts.txt.gz 632.7 Kb (ftp)(http) TXT
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