Egr2, also known as early growth response 2, is a transcription factor that plays crucial roles in multiple biological processes. It is intricately involved in the transcriptional regulatory networks of various cell types, participating in pathways related to immune response, cell differentiation, and tissue repair [1,2,3,4,5,6,7,8]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying Egr2's functions.

T cell-specific deletion of Egr2 attenuated neuroinflammation in mice with autoimmune neuroinflammation without compromising the host's ability to control infections, suggesting Egr2 regulates the pathogenicity of TH17 cells in the central nervous system [1]. EGR2 deficiency in alveolar macrophages led to impaired zymosan internalization and reduced capacity to respond to Aspergillus fumigatus, demonstrating its role in phagocytosis and antifungal immunity [2]. Satellite cell-specific deletion of TECRL enhanced muscle repair by up-regulating EGR2 through the activation of the ERK1/2 signaling pathway, highlighting Egr2's role in myogenic regeneration [3]. Conditional knockout of EGR2 in microglia increased intraocular inflammation in mice, indicating Egr2's protective role in autoimmune uveitis by modulating the microglial phenotype [4]. Egr2-deficiency in mice with metabolic dysfunction-associated steatohepatitis rerouted monocyte differentiation, suppressing the transition from steatosis to liver fibrosis [5]. In lupus-like disease, mice deficient for Egr2 developed dysregulated activation of effector T cells, suggesting Egr2 suppresses excessive immune responses [6]. Inhibition of EGR2 in vitro reduced IFNγ production and Th1 differentiation in lupus CD4+ T cells [7]. EGR2 knockout in CAR T cells blocked type I interferon-mediated inhibitory program and improved their efficacy against tumors [9].

In conclusion, Egr2 is a key transcription factor involved in immune regulation, cell differentiation, and tissue repair. KO/CKO mouse models have revealed its roles in diseases such as autoimmune neuroinflammation, fungal infections, muscle repair, autoimmune uveitis, metabolic-associated liver fibrosis, lupus-like disease, and in modulating the function of CAR T cells, providing insights into disease mechanisms and potential therapeutic targets.