Group 2 innate lymphocytes protect the balance between autophagy and apoptosis in cardiomyocytes during sepsis-induced cardiac injury.

Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p < 0.01), reduced cardiac dysfunction, and lower markers of cardiac injury. Conversely, IL-33 deficiency led to exacerbated cardiac damage. Additionally, heart ILC2 significantly increased the expression and secretion of IL-5 (2.18 ± 0.34 ng/ml vs. 1.18 ± 0.24 ng/ml, p < 0.05) and IL-13 (10.55 ± 1.13 ng/ml vs. 7.59 ± 1.13 ng/ml, p < 0.05) following sepsis, with this response being mediated by IL-33. Moreover, IL-5 deficient mice exhibited increased cardiac dysfunction and myocardial apoptosis post-sepsis (20.7 ± 4.28% vs. 29.61 ± 4.28%, p < 0.05). Furthermore, in vitro experiments involving co-cultures of ILC2 with mice cardiomyocytes after lipopolysaccharide (LPS) administration suggested that IL-5 derived from ILC2 protects cardiomyocytes from autophagy and apoptosis. These findings imply that IL-33, released in response to sepsis, induces ILC2 activation and IL-5 secretion, orchestrating the equilibrium between autophagy and apoptosis in cardiomyocytes and offering potential therapeutic avenues for mitigating sepsis-induced cardiac injury.