CXCR3型
压力过载
趋化因子
心力衰竭
CXCL9型
CXCL10型
趋化因子受体
T细胞
炎症
CX3CR1型
医学
细胞生物学
整合素
免疫学
受体
生物
内科学
免疫系统
心肌肥大
作者
Njabulo Ngwenyama,Ane M. Salvador,Francisco Velázquez,Tania Nevers,Alexander M Levy,Mark Aronovitz,Andrew D. Luster,Gordon S. Huggins,Pilar Alcaide
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2019-04-04
卷期号:4 (7)
被引量:46
标识
DOI:10.1172/jci.insight.125527
摘要
Heart failure (HF) is associated in humans and mice with increased circulating levels of CXCL9 and CXCL10, chemokine ligands of the CXCR3 receptor, predominantly expressed on CD4+ Th1 cells. Chemokine engagement of receptors is required for T cell integrin activation and recruitment to sites of inflammation. Th1 cells drive adverse cardiac remodeling in pressure overload-induced cardiac dysfunction, and mice lacking the integrin ligand ICAM-1 show defective T cell recruitment to the heart. Here, we show that CXCR3+ T cells infiltrate the heart in humans and mice with pressure overload-induced cardiac dysfunction. Genetic deletion of CXCR3 disrupts CD4+ T cell heart infiltration and prevents adverse cardiac remodeling. We demonstrate that cardiac fibroblasts and cardiac myeloid cells that include resident and infiltrated macrophages are the source of CXCL9 and CXCL10, which mechanistically promote Th1 cell adhesion to ICAM-1 under shear conditions in a CXCR3-dependent manner. To our knowledge, our findings identify a previously unrecognized role for CXCR3 in Th1 cell recruitment into the heart in pressure overload-induced cardiac dysfunction.
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