Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/LX22NPO5104" target="_blank" >LX22NPO5104: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

1091-6490

Svazek periodika

121

Číslo periodika v rámci svazku

42

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

"art. no. e2323052121"

Kód UT WoS článku

001349516900004

EID výsledku v databázi Scopus

2-s2.0-85205830519