Il34, interleukin-34, is a cytokine that activates the CSF-1 receptor (CSF-1R) along with colony-stimulating factor-1 (CSF-1). It plays crucial roles in regulating the development of many cell types such as most tissue macrophages, osteoclasts, Langerhans cells, Paneth cells, and brain microglia. It is also involved in the differentiation of neural progenitor cells and functions in the female reproductive tract [1]. Gene knockout models are valuable for studying Il34's function.

In a global and conditional knockout mouse model, deletion of Il34 led to muscle regeneration defects as it sustained satellite cell (SC) expansion at the cost of differentiation. Inactivating Il34 in SCs hyperactivated NFKB1 signaling, disturbing Akt activity, and disrupting Akt mimicked the Il34 knockout phenotype. Deleting Il34 in mdx mice ameliorated dystrophic muscles, indicating its role in muscle homeostasis [2].

In p53-inactivated liver cancer, Il34, a gene transcriptionally repressed by p53, was secreted by cancer stem cells (CSCs) upon p53 loss. IL-34 induced M2-like polarization of tumor-associated macrophages (TAMs), suppressing CD8+ T cell-mediated antitumor immunity. Blockade of the IL-34-CD36 axis elicited antitumor immunity [3].

In hepatocellular carcinoma, IL34+ cancer-associated fibroblasts (CAFs) promoted Tregs infiltration, suppressed CD8+ T cell toxicity, and enhanced HCC growth and metastasis [4].

In myocardial ischemic/reperfusion injury, IL-34 knockout mitigated cardiac remodeling, dysfunction, and fibrosis. IL-34 deficiency repressed the NF-κB signaling pathway, reducing macrophage recruitment and polarization [5].

In conclusion, Il34 is essential in various biological processes. Its deletion in KO/CKO mouse models has revealed its significance in muscle regeneration, tumor immune escape, hepatocellular carcinoma progression, and myocardial ischemic/reperfusion injury. These findings suggest that targeting Il34 could potentially be a therapeutic strategy in related disease areas.