["\n\n\n\n\n\n\n\n\n\n\nAbstract\n\nAim\nThe imbalance of T helper (Th) 17/T regulatory (Treg) is involved in chronic heart failure (HF). The enzyme lysyl oxidase (LOX) contributes to myocardial fibrosis. This study was designed to decipher the regulatory mechanism of Th17/Treg on LOX expression and to validate whether Th17/Treg imbalance regulates myocardial fibrosis by modulating LOX expression.\n\n\nMethods\nHuman cardiac fibroblasts (HCFs) were treated with angiotensin II (Ang II) and co‐cultured with Th17 cells and Tregs which were polarized from control naïve CD4+ T cells. Th17 cells and Tregs were adoptively transferred into abdominal aortic coarctation‐induced chronic HF rats to investigate the efficacy of Th17 and Treg infusions on myocardial fibrosis and HF.\n\n\nResults\nTh17/Treg imbalance (increased Th17 cells and decreased Tregs) was observed in HF patients. Th17 cells/Tregs aggravated/attenuated Ang II‐induced upregulation of LOX and fibrosis‐related indicators (MMP‐2/9 and collagen I/III) in HCFs in vitro and abdominal aortic coarctation‐induced myocardial fibrosis and HF in rats, by promoting/inhibiting LOX expression. Mechanistically, Th17 cells promoted LOX expression by activating the IL‐17/ERK1/2‐AP‐1 pathway, while Tregs inhibited LOX expression by activating the IL‐10/JAK1‐STAT3 pathway.\n\n\nConclusion\nIncreased Th17 cells and decreased Tregs aggravate myocardial fibrosis and HF by inducing LOX expression.\n\n", "Acta Physiologica, Volume 230, Issue 3, November 2020. "]