Ngwenyama Njabulo, Kaur Kuljeet, Bugg Darrian, Theall Brandon, Aronovitz Mark, Berland Robert, Panagiotidou Smaro, Genco Caroline, Perrin Mercio A, Davis Jennifer, Alcaide Pilar
Department of Immunology, Tufts University, Boston, MA, USA.
Departments of Lab Medicine-Pathology & Bioengineering, University of Washington, Seattle, WA, USA.
Nat Cardiovasc Res. 2022 Aug;1(8):761-774. doi: 10.1038/s44161-022-00116-7. Epub 2022 Aug 12.
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 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.
心力衰竭（HF）是发病和死亡的主要原因。对动物模型和HF患者的研究揭示了CD4 + T细胞免疫反应在HF发病机制中的重要作用，并突出了心脏成纤维细胞与产生IFNγ的CD4 + T细胞之间的活跃串扰，这导致了促纤维化的肌成纤维细胞转化。心脏成纤维细胞是否同时调节致病性心脏CD4 + T细胞免疫反应尚不清楚。在这里，我们报告在两种不同的心脏炎症实验模型中，小鼠心脏成纤维细胞表达主要组织相容性复合体II类（MHCII）。我们证明心脏成纤维细胞摄取和处理抗原，通过IFNγ诱导的MHCII呈递给CD4 + T细胞。心脏成纤维细胞中 的条件性缺失改善了心脏压力过载诱导的心脏重塑和功能障碍。总体而言，我们证明心脏成纤维细胞作为抗原呈递细胞（APC）发挥作用，并通过IFNγ诱导的MHCII促进心脏纤维化和功能障碍。
