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| Status |
Public on Nov 24, 2023 |
| Title |
GPR15-mediated T cell recruitment during acute viral myocarditis facilitated virus elimination and improved outcome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Viral myocarditis is characterised by infiltration of mononuclear cells essential for virus elimination. GPR15 has been identified as a homing receptor for regulatory T cells in inflammatory intestine diseases, but its role in inflammatory heart diseases is still elusive. Therefore, we investigated the role of GPR15 during coxsackievirus B3‑induced myocarditis utilizing GPR15‑deficient mice as well as using in vitro experiments. Here we show that GPR15 deficiency had no effect on susceptibility to virus infection, but virus elimination was scant leading to adverse cardiac remodelling and impaired cardiac function. Delayed recruitment of regulatory T cells was accompanied by prolonged persistence of cytotoxic T cells as well as regulatory T cells in GPR15-deficient mice. Further, RNA sequencing revealed prolonged inflammatory response and altered chemotaxis in GPR15-deficient mice. In line, we identified GPR15 and its ligand GPR15L as an important chemokine receptor-ligand pair for the recruitment of regulatory and cytotoxic T cells. In summary, the insufficient virus elimination might be caused by a delayed recruitment of T cells as well as delayed interferon-γ expression, resulting in a prolonged inflammatory response and an adverse outcome in GPR15-deficient mice.
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| Overall design |
Heart tissue from GPR15 deficient and wildtype mice were investigated either with CVB3 induced myocarditis or controls
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| Web link |
https://doi.org/10.1038/s44161-023-00401-z
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| Contributor(s) |
Lindner D |
| Citation missing |
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| |
| Submission date |
Nov 23, 2023 |
| Last update date |
Feb 23, 2024 |
| Contact name |
Diana Lindner |
| E-mail(s) |
diana.lindner@uniklinik-freiburg.de
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| Organization name |
University Hospital Freiburg
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| Department |
University Heart Center Freiburg-Bad Krozingen
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| Street address |
Hugstetter Straße 55
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA1044422 |
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