Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00085072" target="_blank" >RIV/00023001:_____/24:00085072 - isvavai.cz</a>
Result on the web
<a href="https://www.pnas.org/doi/10.1073/pnas.2323052121" target="_blank" >https://www.pnas.org/doi/10.1073/pnas.2323052121</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1073/pnas.2323052121" target="_blank" >10.1073/pnas.2323052121</a>
Alternative languages
Result language
angličtina
Original language name
Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis
Original language description
Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (T(RM)) cells, we characterized cardiac T(RM) cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC T(RM) cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC T(RM) cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human T(RM) cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69(+) T(RM) cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial T(RM) cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
<a href="/en/project/LX22NPO5104" target="_blank" >LX22NPO5104: National Institute for Research of Metabolic and Cardiovascular Diseases</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
e-ISSN
1091-6490
Volume of the periodical
121
Issue of the periodical within the volume
42
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
"art. no. e2323052121"
UT code for WoS article
001349516900004
EID of the result in the Scopus database
2-s2.0-85205830519