Irf8, also known as interferon regulatory factor 8, is a transcription factor of the IRF protein family. It is essential for myeloid cell lineage commitment and differentiation, and is involved in pathways like antigen processing and presentation, cytokine and chemokine expression, and response to various stimuli. It plays a crucial role in the immune system, influencing the development and function of immune cells [2,4]. Genetic models, such as gene knockout (KO) mouse models, have been valuable in studying its functions.

In KO mouse models, deletion of Irf8 leads to massive accumulation of CD11b+Gr1+ immature myeloid cells, particularly polymorphonuclear myeloid-derived suppressor cell-like cells, which can promote tumor immune evasion [2]. In breast cancer murine models, TAM-specific Irf8 deletion prevented exhaustion of cancer-cell-reactive CTLs and suppressed tumor growth, indicating that Irf8 in tumor-associated macrophages promotes T cell exhaustion [1]. In microglia, constitutive and postnatal Irf8 deletion led to a loss of microglia identity, gain of disease-associated microglia-like genes, and reduced interaction with amyloidβ plaques in the 5xFAD model [3].

In conclusion, Irf8 is vital for the development and function of immune cells and plays a role in multiple biological processes. Studies using Irf8 KO/CKO mouse models have revealed its significance in cancer, where it can impact tumor growth through T cell exhaustion, and in microglia-related diseases like those associated with amyloidβ plaques. These findings enhance our understanding of disease mechanisms and may offer potential therapeutic targets.