Ifi30-flox Mouse

Ifi30, encoding gamma-interferon-inducible lysosomal thiol reductase, is a key enzyme mainly present in immune cells. It functions in reducing protein disulfide bonds in endocytosis-mediated protein degradation, and is involved in antigen presentation and immune regulation, such as in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation pathways of adaptive immunity [2,4]. It also participates in immune-related signaling pathways like peptide antigen binding, cytokine binding, and MHC class II presentation [1].

In gliomas, high Ifi30 expression is associated with malignancy and poor outcomes. Univariable and multivariable Cox regression analyses defined it as an independent prognostic marker. Samples with higher Ifi30 expression have higher infiltration of immune cells including regulatory T cells and M0 macrophages, and it is significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses [2]. In breast cancer, Ifi30 expression is upregulated in cancer tissues compared to normal ones, related to tumor stage and prognosis. Ectopic knockdown of Ifi30 in tumor cells and macrophages reduces PD-L1 expression, while overexpression increases it, suggesting its interplay with the PD-L1 axis [1]. In zebrafish, morpholino-mediated Ifi30 knockdown leads to incomplete caudal vein plexus (CVP) formation with reduced loop numbers, area, and width, indicating its role in sprouting angiogenesis during CVP formation [3].

In conclusion, Ifi30 plays essential roles in immune regulation, angiogenesis, and tumor-related processes. Studies on Ifi30, including those using loss-of-function models in zebrafish and its analysis in human cancer tissues, have provided insights into its functions in disease conditions such as glioma and breast cancer, highlighting its potential as a prognostic biomarker and therapeutic target.