Interleukin-10 stiffens the heart

Abstract

Cardiac-resident macrophages are a diverse population of cells that have a critical role in the pathogenesis of heart failure. A new understanding of communication between macrophages and cardiac fibroblasts could lead to novel therapeutic strategies for heart failure with preserved ejection function.

Insight from Daniela Cihakova

(A) MHCII^high cardiac-resident macrophage–derived IL-10 induces autocrine macrophage differentiation toward a profibrotic phenotype. Profibrotic macrophages produce OPN. OPN activates cardiac fibroblasts to promote collagen deposition, which results in fibrosis and increased cardiac stiffness. (B) MHCII^low macrophages contribute to extracellular matrix breakdown by their MMP production. (C) Cardiac fibroblasts also affect myeloid cells trafficking to the heart by secreting chemokines, cytokines, and growth factors, such as CCL2, GM-CSF, and CCL11 after cardiac injury.