Heart failure (HF) is a leading cause of morbidity and mortality. Studies in animal models and individuals with HF revealed a prominent role for CD4⁺ T cell immune responses in the pathogenesis of HF and highlighted an active cross-talk between cardiac fibroblasts and interferon (IFN)-γ-producing CD4⁺ T cells that results in profibrotic myofibroblast transformation. Whether cardiac fibroblasts concomitantly modulate pathogenic cardiac CD4⁺ T cell immune responses is unknown. Recently, the researchers report that mouse cardiac fibroblasts express major histocompatibility complex type II (MHCII) in two different experimental models of cardiac inflammation. The researchers demonstrate that cardiac fibroblasts take up and process antigens for presentation to CD4⁺ T cells via MHCII induced by IFN-γ. Conditional deletion of MhcII in cardiac fibroblasts ameliorates cardiac remodeling and dysfunction induced by cardiac pressure overload. Collectively, the researchers demonstrate that cardiac fibroblasts function as antigen-presenting cells and contribute to cardiac fibrosis and dysfunction through MHCII induced by IFN-γ.

@Njabulo Ngwenyama, et al.

Figure 1. IFN-γ produced by TH1 cells induces MHCII expression by cardiac fibroblasts and promotes antigen-specific CD4⁺ T cell activation.

Source from:

Ngwenyama N, Kaur K, Bugg D, et al. Antigen presentation by cardiac fibroblasts promotes cardiac dysfunction. Nature Cardiovascular Research 2022; 1: 761-774. doi: 10.1038.s44161-022-00116-7.