T cell-derived adenosine regulates fibroblast IL-6 formation via A2B receptors in the infarcted heart

TL;DR

This study shows how T cells and heart fibroblasts interact to increase inflammation after a heart attack.

Contribution

The study identifies T cell-derived adenosine as a novel regulator of IL-6 production in cardiac fibroblasts after myocardial infarction.

Findings

Cardiac fibroblasts are the main source of IL-6 after a heart attack.

T cells produce adenosine via CD73, which activates fibroblasts to make more IL-6.

The adenosine-A2B receptor-IL6 pathway is a potential target for reducing heart inflammation.

Abstract

Elevated interleukin-6 (IL-6) levels are linked to an increased risk of cardiovascular mortality in myocardial infarction (MI). Targeting IL-6 and its downstream signalling pathways represents a therapeutic strategy; however, its cellular sources and regulatory mechanisms of IL-6 remain incompletely understood. In this study, Alter and colleagues investigated the primary cell type that produces IL-6 in post-MI murine heart and the role of purinergic signalling in regulating IL-6 formation. Using cellular and mouse models, the authors identified cardiac fibroblasts as the predominant source of IL-6. Further analysis revealed that the IL-6 formation in cardiac fibroblasts is regulated by adenosine A2B receptors. Of further importance, they elucidated that T cells highly express CD73, leading to significant adenosine formation, which in turn enhances IL-6 production via Gq activation in cardiac fibroblasts following MI. These findings reveal a dynamic interplay between immune cells and fibroblasts in shaping the post-MI inflammatory response. This study suggests the adenosine-A2B receptor-IL6 axis as a potential therapeutic target to mitigate inflammation and improve cardiomyocytes salvage in MI.

Figures