New role for interleukin-13 receptor α1 in myocardial homeostasis and heart failure

Background- the immune system plays a pivotal role in myocardial homeostasis and response to injury. interleukins-4 and -13 are anti-inflammatory type-2 cytokines,signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. the role of interleukin-13 receptor α1 in the heart is unknown. methods and results- we analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). we found that the interleukin-13 receptor α1 is present in the myocardium and,together with the complementary type-2 interleukin-4 receptor chain il4ra,is significantly downregulated in the hearts of patients with heart failure. next,we showed that il13ra1-deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; p=0.004,left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; p=0.03). a bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system,such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery rate q=0). deficiency of il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions. conclusions- the results of our studies in humans and mice indicate,for the first time,a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. © 2017 the authors.