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Series GSE228682 Query DataSets for GSE228682
Status Public on Oct 03, 2023
Title Effector Memory T cells induce DC-intrinsic DNA damage and a non-canonical STING pathway during innate inflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary A breach in tolerance to self-antigens induces expansion of autoreactive T cells, ultimately leading to autoimmune inflammation. While autoreactive T cells are principal drivers of autoimmunity, tissue pathology is alternatively driven by innate cytokines, indicating that autoreactive T cells can induce innate inflammation. This study has led to the discovery that effector memory T (Tem) cells trigger double stranded breaks via mitochondrial ROS production in interacting DCs. Consequently, initiation of the DNA damage response leads to activation of a cGAS-independent, STING-TRAF6-NFkB signaling axis. STING deficient DCs display significant defects in transcriptional induction and functional production of IL-1b and IL-6 following their interaction with Tem cells, both in vitro and in vivo. The discovery of Tem induced innate inflammation through DNA damage and a non-canonical STING-mediated NFkB activation presents this pathway as a potential target to alleviate T cell driven autoimmune inflammation.
Overall design WT or STING golden ticket BMDCs were co-cultured with in vitro generated effector memory T (Tem) cells + anti-CD3 for 1 hour. BMDCs were then sorted away from Tem cells and submitted for sequencing. Control samples include WT and STING golden ticket sorted BMDCs previously cultured with Tem cells - anti-CD3 (unstimulated).
Contributor(s) Meibers HE, Pasare C
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Submission date Mar 31, 2023
Last update date Oct 03, 2023
Contact name Chandrashekhar Pasare
Organization name Cincinnati Children's Hospital Medical Center
Department Immunology
Lab Chandrashekhar Pasare
Street address 250 Albert Sabin Way
City Cincinnati
State/province Ohio
ZIP/Postal code 45229
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (12)
GSM7134875 sorted WT BMDCs, +Tem unstimulated control 1
GSM7134876 sorted WT BMDCs, +Tem unstimulated control 2
GSM7134877 sorted WT BMDCs, +Tem unstimulated control 3
BioProject PRJNA950996

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Supplementary file Size Download File type/resource
GSE228682_rna_counts_matrix.txt.gz 548.5 Kb (ftp)(http) TXT
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