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CXCR3 regulates CD4+ T cell cardiotropism in pressure overload-induced cardiac dysfunction.
- Source :
-
JCI insight [JCI Insight] 2019 Apr 04; Vol. 4 (7). Date of Electronic Publication: 2019 Apr 04 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Animals
Blood Pressure
Chemokine CXCL10 immunology
Chemokine CXCL10 metabolism
Chemokine CXCL9 immunology
Chemokine CXCL9 metabolism
Disease Models, Animal
Echocardiography
Fibroblasts
Heart Failure diagnosis
Heart Failure pathology
Humans
Intercellular Adhesion Molecule-1 immunology
Intercellular Adhesion Molecule-1 metabolism
Macrophages
Male
Mice
Myocardium cytology
Myocardium pathology
Myofibroblasts
Receptors, CXCR3 immunology
Th1 Cells metabolism
Heart Failure immunology
Myocardium immunology
Receptors, CXCR3 metabolism
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 4
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 30779709
- Full Text :
- https://doi.org/10.1172/jci.insight.125527