Antigen presentation by cardiac fibroblasts promotes cardiac dysfunction.

Area of Science:

• Immunology
• Cardiology
• Fibrosis Research

Background:

• Heart failure (HF) involves CD4+ T cells and cardiac fibroblasts, with known crosstalk leading to fibrosis.
• The role of cardiac fibroblasts in modulating T cell responses during HF pathogenesis remains unclear.

Purpose of the Study:

• To investigate whether cardiac fibroblasts influence pathogenic cardiac CD4+ T cell immune responses.
• To determine if cardiac fibroblasts act as antigen-presenting cells (APCs) in cardiac inflammation.

Main Methods:

• Murine models of cardiac inflammation and pressure overload.
• Assessment of major histocompatibility complex type II (MHCII) expression on cardiac fibroblasts.
• Analysis of antigen uptake and presentation by cardiac fibroblasts to CD4+ T cells.
• Conditional deletion of MHCII in cardiac fibroblasts to evaluate functional impact.

Main Results:

• Murine cardiac fibroblasts express MHCII during cardiac inflammation.
• Cardiac fibroblasts process antigens and present them to CD4+ T cells via IFNγ-induced MHCII.
• Conditional deletion of MHCII in cardiac fibroblasts improved cardiac remodeling and function under pressure overload.

Conclusions:

• Cardiac fibroblasts function as antigen-presenting cells (APCs) in the context of cardiac inflammation.
• IFNγ-induced MHCII expression enables cardiac fibroblasts to modulate CD4+ T cell responses.
• Cardiac fibroblasts contribute to HF-associated fibrosis and dysfunction by presenting antigens via MHCII.