Stat1, short for Signal transducer and activator of transcription 1, is a latent cytoplasmic transcription factor. It is a crucial component in the interferon (IFN)-signaling pathway, transducing signals from type I, II, and III IFNs to the nucleus [3,4]. This pathway impacts various biological processes, such as immune response, cell cycle, and cell survival [2]. The IFN-γ/STAT1 immune signaling pathway has non-canonical neuron-specific functions beyond its role in controlling intracellular pathogens [1].

Gene knockout (KO) and conditional knockout (CKO) mouse models have been instrumental in understanding Stat1's role. STAT1 gene deletion in mice causes rapid death from severe infections, highlighting its key role in the immune response against viruses and other pathogens [4]. Inborn errors of human STAT1 immunity, which can be modeled in mice, underlie 4 distinct disorders with different clinical manifestations, reflecting the complex roles of STAT1 in host immune systems [3].

In conclusion, Stat1 is essential for the immune response, especially against viral infections. Studies using KO and CKO mouse models have revealed its significance in maintaining immune homeostasis and the consequences of its dysfunction in various disease conditions, such as inborn errors of immunity [3,4].

References:

1. Clark, Danielle N, Begg, Lauren R, Filiano, Anthony J. 2022. Unique aspects of IFN-γ/STAT1 signaling in neurons. In Immunological reviews, 311, 187-204. doi:10.1111/imr.13092. https://pubmed.ncbi.nlm.nih.gov/35656941/

2. Butturini, Elena, Carcereri de Prati, Alessandra, Mariotto, Sofia. 2020. Redox Regulation of STAT1 and STAT3 Signaling. In International journal of molecular sciences, 21, . doi:10.3390/ijms21197034. https://pubmed.ncbi.nlm.nih.gov/32987855/

3. Mizoguchi, Yoko, Okada, Satoshi. 2021. Inborn errors of STAT1 immunity. In Current opinion in immunology, 72, 59-64. doi:10.1016/j.coi.2021.02.009. https://pubmed.ncbi.nlm.nih.gov/33839590/

4. Tolomeo, Manlio, Cavalli, Andrea, Cascio, Antonio. 2022. STAT1 and Its Crucial Role in the Control of Viral Infections. In International journal of molecular sciences, 23, . doi:10.3390/ijms23084095. https://pubmed.ncbi.nlm.nih.gov/35456913/