Il12a, encoding the interleukin-12 p35 subunit, is crucial for immune responses. Interleukin-12 (IL-12) is a cytokine that plays a key role in the activation of T cells and natural killer (NK) cells, driving Th1 cell differentiation and enhancing cell-mediated immunity [2]. It is involved in multiple pathways related to inflammation, host defense, and anti-tumor immunity. Genetic models, such as gene knockout mice, have been instrumental in studying its function.

In a study using Il12a knockout mice, Il12a deletion was found to aggravate sepsis-induced cardiac dysfunction. Macrophages, the main source of Il12a, showed an enhanced M1 phenotype accumulation after Il12a deletion in lipopolysaccharide (LPS)-treated mice. This led to increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB), indicating more severe cardiac injury. Also, Il12a deletion 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). Treatment with the AMPK activator AICAR abolished the deterioration effect of Il12a deletion on LPS-induced cardiac dysfunction [1]. In another study, myeloid-specific Mef2c-knockout mice, which showed reduced IL-12 production due to downregulated Il12a and Il12b expression, were more susceptible to Listeria monocytogenes infection and protected against DSS-induced IBD, highlighting the role of Il12a in macrophage polarization and Th1 responses [2].

In conclusion, Il12a is essential for proper immune responses, especially in macrophage polarization and Th1 cell-mediated immunity. Studies using Il12a knockout mouse models have revealed its significance in sepsis-induced cardiac dysfunction, as well as in infectious and inflammatory diseases like Listeria monocytogenes infection and DSS-induced IBD. Understanding Il12a's function can potentially provide new therapeutic targets for these disease areas.

References:

1. Wang, Zhen, Liu, Menglin, Ye, Di, Li, Dan, Wan, Jun. 2021. Il12a Deletion Aggravates Sepsis-Induced Cardiac Dysfunction by Regulating Macrophage Polarization. In Frontiers in pharmacology, 12, 632912. doi:10.3389/fphar.2021.632912. https://pubmed.ncbi.nlm.nih.gov/34276358/

2. Zhao, Xibao, Di, Qianqian, Liu, Han, An, Huazhang, Chen, Weilin. 2022. MEF2C promotes M1 macrophage polarization and Th1 responses. In Cellular & molecular immunology, 19, 540-553. doi:10.1038/s41423-022-00841-w. https://pubmed.ncbi.nlm.nih.gov/35194174/