Loading…

Central role of PD-L1 in cardioprotection resulting from P2Y4 nucleotide receptor loss

A better understanding of the immune function of pericardial adipose tissue is essential to adapt treatments after myocardial infarction. We showed previously that inactivation of mouse P2Y 4 nucleotide receptor induces adiponectin overexpression and protection against myocardial infarction. We inve...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2022-09, Vol.13, p.1006934-1006934
Main Authors: Horckmans, Michael, Diaz Villamil, Esteban, Bianchini, Mariaelvy, De Roeck, Lucas, Communi, Didier
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A better understanding of the immune function of pericardial adipose tissue is essential to adapt treatments after myocardial infarction. We showed previously that inactivation of mouse P2Y 4 nucleotide receptor induces adiponectin overexpression and protection against myocardial infarction. We investigated here the inflammatory state of pericardial adipose tissue in ischemic P2Y 4 -deficient mice. We demonstrated that P2Y 4 -deficient mice displayed adipocyte beiging with increased PD-L1 expression and a higher number of regulatory leukocytes in their pericardial adipose tissue after left anterior descending artery ligation, compared to wild type mice. Effectively, a higher level of anti-inflammatory M2c macrophages and regulatory T cells was observed in pericardial adipose tissue of P2Y 4 KO mice and correlated with reduced post-ischemic expansion of fat-associated lymphoid clusters. Interestingly, the anti-inflammatory effects observed in P2Y 4 KO mice, were no more observed in P2Y 4 /adiponectin double KO ischemic mice. Finally, the reduction of T cell infiltration and cardiac fibrosis observed in P2Y 4 -deficient heart was lost after injection of anti-PD-L1 blocking antibody in ischemic mice. The present study defines P2Y 4 as a regulator of PD-L1 and adiponectin, and as a potential target for anti-inflammatory therapies to improve myocardial infarction outcome. The combined effect of P2Y 4 loss on adipocyte beiging and regulatory leukocyte increase highlights this nucleotide receptor as an important player in post-ischemic cardiac response.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.1006934