Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression.
AIM
The 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.


METHODS
Human 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.


RESULTS
Th17/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.


CONCLUSION
Increased Th17 cells and decreased Tregs aggravate myocardial fibrosis and HF by inducing LOX expression.
['Lu|Min|M|', 'Qin|Xinglei|X|0000-0001-6295-6401', 'Yao|Jungong|J|', 'Yang|Yuanyuan|Y|', 'Zhao|Minghu|M|', 'Sun|Lin|L|']
D000818:Animals D005355:Fibrosis D006333:Heart Failure D006801:Humans D008249:Protein-Lysine 6-Oxidase D051381:Rats D050378:T-Lymphocytes, Regulatory D058504:Th17 Cells
Th17 Treg heart failure LOX cardiac fibrosis