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| 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.
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| 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).
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| Contributor(s) |
Meibers HE, Pasare C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 31, 2023 |
| Last update date |
Oct 03, 2023 |
| Contact name |
Chandrashekhar Pasare |
| E-mail(s) |
Chandrashekhar.pasare@cchmc.org
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| Organization name |
Cincinnati Children's Hospital Medical Center
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| Department |
Immunology
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| Lab |
Chandrashekhar Pasare
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| Street address |
250 Albert Sabin Way
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| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| GSM7134875 |
sorted WT BMDCs, +Tem unstimulated control 1 |
| GSM7134876 |
sorted WT BMDCs, +Tem unstimulated control 2 |
| GSM7134877 |
sorted WT BMDCs, +Tem unstimulated control 3 |
| GSM7134878 |
sorted WT BMDCs, +Tem+anti-CD3 stimulated 1hr 1 |
| GSM7134879 |
sorted WT BMDCs, +Tem+anti-CD3 stimulated 1hr 2 |
| GSM7134880 |
sorted WT BMDCs, +Tem+anti-CD3 stimulated 1hr 3 |
| GSM7134881 |
sorted STINGgt/gt BMDCs, +Tem unstimulated control 1 |
| GSM7134882 |
sorted STINGgt/gt BMDCs, +Tem unstimulated control 2 |
| GSM7134883 |
sorted STINGgt/gt BMDCs, +Tem unstimulated control 3 |
| GSM7134884 |
sorted STINGgt/gt BMDCs, +Tem+anti-CD3 stimulated 1hr 1 |
| GSM7134885 |
sorted STINGgt/gt BMDCs, +Tem+anti-CD3 stimulated 1hr 2 |
| GSM7134886 |
sorted STINGgt/gt BMDCs, +Tem+anti-CD3 stimulated 1hr 3 |
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| Relations |
| BioProject |
PRJNA950996 |
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