Antigen presentation by cardiac fibroblasts promotes cardiac dysfunction

Nat Cardiovasc Res. 2022 Aug;1(8):761-774. doi: 10.1038/s44161-022-00116-7. Epub 2022 Aug 12.

Abstract

Heart failure (HF) is a leading cause of morbidity and mortality. Studies in animal models and patients with HF revealed a prominent role for CD4+ T cell immune responses in the pathogenesis of HF and highlighted an active crosstalk between cardiac fibroblasts and IFNγ producing CD4+ T cells that results in profibrotic myofibroblast transformation. Whether cardiac fibroblasts concomitantly modulate pathogenic cardiac CD4+ T cell immune responses is unknown. Here we show report that murine cardiac fibroblasts express major histocompatibility complex type II (MHCII) in two different experimental models of cardiac inflammation. We demonstrate that cardiac fibroblasts take up and process antigens for presentation to CD4+ T cells via MHCII induced by IFNγ. Conditional deletion of MhcII in cardiac fibroblasts ameliorates cardiac remodelling and dysfunction induced by cardiac pressure overload. Collectively, we demonstrate that cardiac fibroblasts function as antigen presenting cells (APCs) and contribute to cardiac fibrosis and dysfunction through IFNγ induced MHCII.