Il12a, encoding the interleukin-12 p35 subunit, is a crucial gene in the immune-regulatory network. Interleukin-12 (IL-12) is a cytokine that plays a vital role in the activation of T cells and natural killer (NK) cells, promoting the differentiation of Th1 cells, and thus is involved in cell-mediated immunity pathways. It is of great biological importance for the body's defense against pathogens and in immune-related diseases [2].

In a sepsis-related study, Il12a knockout mice were used to explore its role. Il12a deletion was found to aggravate lipopolysaccharide (LPS)-induced cardiac dysfunction and injury, accompanied by increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). The deletion also enhanced LPS-induced macrophage accumulation and drove macrophages toward the M1 phenotype, downregulated the activity of AMP-activated protein kinase (AMPK), but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). Similarly, Il12a deletion aggravated cecal ligation and puncture (CLP)-induced cardiac dysfunction and injury. This indicates that Il12a plays a protective role in sepsis-induced cardiac dysfunction by regulating macrophage polarization [1].

In conclusion, Il12a is essential for immune-regulatory functions, especially in promoting Th1 cell-mediated immunity. The use of Il12a knockout mouse models has provided clear evidence of its role in sepsis-induced cardiac dysfunction, suggesting it could be a potential target for treating this condition. This highlights the importance of genetic models in understanding Il12a's function in disease-related biological processes.