GPR15-mediated T cell recruitment during acute viral myocarditis facilitated virus elimination and improved outcome.
Animals
Myocarditis
/ immunology
Receptors, G-Protein-Coupled
/ genetics
Mice, Knockout
Coxsackievirus Infections
/ immunology
Disease Models, Animal
Enterovirus B, Human
/ immunology
Mice, Inbred C57BL
T-Lymphocytes, Regulatory
/ immunology
Acute Disease
Interferon-gamma
/ metabolism
Mice
T-Lymphocytes, Cytotoxic
/ immunology
Male
Chemotaxis, Leukocyte
/ genetics
Myocardium
/ metabolism
Signal Transduction
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
07
09
2022
accepted:
27
11
2023
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Viral myocarditis is characterized 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. Here we show that GPR15 deficiency impairs coxsackievirus B3 elimination, leading to adverse cardiac remodeling and dysfunction. Delayed recruitment of regulatory T cells in GPR15-deficient mice was accompanied by prolonged persistence of cytotoxic and regulatory T cells. In addition, RNA sequencing revealed prolonged inflammatory response and altered chemotaxis in knockout 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.
Identifiants
pubmed: 39195892
doi: 10.1038/s44161-023-00401-z
pii: 10.1038/s44161-023-00401-z
doi:
Substances chimiques
Receptors, G-Protein-Coupled
0
Interferon-gamma
82115-62-6
IFNG protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
76-93Subventions
Organisme : Deutsches Zentrum für Herz-Kreislaufforschung (Deutsches Zentrum für Herz-Kreislaufforschung e.V.)
ID : 81Z0710108
Organisme : Deutsches Zentrum für Herz-Kreislaufforschung (Deutsches Zentrum für Herz-Kreislaufforschung e.V.)
ID : 81Z0710108
Informations de copyright
© 2023. The Author(s).
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