Elf4, also known as E74-like factor 4, is a member of the ETS family of transcription factors. It is highly expressed in normal human hematopoietic tissue, ovary, placenta, colon, and certain pathological cell lines. During normal physiological processes, Elf4 regulates differentiation in osteogenic, adipocyte, and neuronal types, and exerts a critical impact on the development of the immune system [3].

In disease-related studies, Elf4 deficiency has been recognized as a novel inborn error of immunity. Pediatric males with Elf4 deficiency often present with recurrent and prolonged oral ulcer, abdominal pain, and diarrhea [2]. In mouse models, intestinal Elf4 deletion exacerbates alcoholic liver disease by disrupting gut homeostasis, as it leads to intestinal barrier dysfunction, gut microbiota dysbiosis, and exaggerated hepatic inflammation and steatosis upon alcohol exposure [4]. In macrophages, Elf4 both sustains the expression of anti-inflammatory genes, such as Il1rn, and limits the upregulation of inflammation amplifiers. Blockade of Trem1 can reverse inflammation and intestine pathology in mice carrying patient-derived variants in Elf4 [1].

In conclusion, Elf4 is crucial for normal physiological processes, especially in immune system development and cell differentiation. Mouse models, especially those with Elf4 deficiency, have revealed its significant role in diseases like inborn errors of immunity, alcoholic liver disease, and inflammatory bowel-like conditions. Understanding Elf4 can potentially provide new therapeutic strategies for these diseases.

References:

1. Tyler, Paul M, Bucklin, Molly L, Zhao, Mengting, Muise, Aleixo M, Lucas, Carrie L. 2021. Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation. In Nature immunology, 22, 1118-1126. doi:10.1038/s41590-021-00984-4. https://pubmed.ncbi.nlm.nih.gov/34326534/

2. Du, Hong-Qiang, Zhao, Xiao-Dong. 2024. Current understanding of ELF4 deficiency: a novel inborn error of immunity. In World journal of pediatrics : WJP, 20, 444-450. doi:10.1007/s12519-024-00807-0. https://pubmed.ncbi.nlm.nih.gov/38733460/

3. Hu, Dian, Zhang, Zerui, Wang, Yijun, Huang, Wenjie, Xia, Limin. 2024. Transcription factor ELF4 in physiology and diseases: Molecular roles and clinical implications. In Genes & diseases, 12, 101394. doi:10.1016/j.gendis.2024.101394. https://pubmed.ncbi.nlm.nih.gov/40083328/

4. Liu, Tongtong, Yu, Haitao, Zhang, Zeming, Yang, Long, You, Fuping. 2022. Intestinal ELF4 Deletion Exacerbates Alcoholic Liver Disease by Disrupting Gut Homeostasis. In International journal of molecular sciences, 23, . doi:10.3390/ijms23094825. https://pubmed.ncbi.nlm.nih.gov/35563234/