Il34, interleukin-34, is a cytokine that activates the CSF-1 receptor (CSF-1R), along with colony-stimulating factor-1 (CSF-1). It plays important roles in development and innate immunity by regulating the development of macrophages, osteoclasts, Langerhans cells, Paneth cells, and brain microglia [1]. It is also involved in the differentiation of neural progenitor cells and functions in the female reproductive tract.

In gene knockout studies, inactivating IL34 in satellite cells of mice led to hyperactivation of NFKB1 signaling, disturbing protein kinase B (Akt) activity. This caused a shift towards satellite cell expansion at the cost of differentiation, resulting in muscle regeneration defects. However, in mdx mice (a model for Duchenne muscular dystrophy), deleting IL34 or interfering with Akt ameliorated dystrophic muscles [2]. In a p53-inactivated liver cancer mouse model, IL34 secreted by cancer stem cells induced M2-like polarization of tumor-associated macrophages, promoting tumor immune escape. Blockade of the IL34-CD36 axis elicited antitumor immunity [3]. In the context of myocardial ischemic/reperfusion injury, IL34 knockout mitigated cardiac remodeling, dysfunction, and fibrosis by attenuating macrophage recruitment and CCR2+ macrophage polarization through repression of the NF-κB signaling pathway [4].

In conclusion, Il34 has diverse functions in biological processes such as muscle regeneration, cancer development, and cardiac injury response. Gene knockout mouse models have been crucial in revealing its role in these disease-related processes, highlighting its potential as a therapeutic target in muscular dystrophy, cancer, and myocardial ischemic/reperfusion injury.