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It functions primarily as a transcriptional repressor through competitive DNA binding and the recruitment of histone-modifying complexes. More recently, NFIL3 has emerged as a critical regulator of immunity. It is essential for the development of multiple immune cell subsets, including NK cells and CD8+ dendritic cells, and modulates the activity of many others. For instance, NFIL3 influences B cell class switching and cytokine production in T helper subsets and macrophages. Its expression is dynamically controlled by cytokines and environmental signals, positioning NFIL3 as a key integrator of circadian and immune pathways. Consistent with these roles, recent studies have implicated NFIL3 in multiple immune-mediated diseases, including colitis, lupus, and arthritis. In this review, we highlight NFIL3\u2019s immunological functions, its evolutionary conservation, and its emerging role as a context-dependent modulator of inflammation and immune homeostasis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag103","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:47:33Z","timestamp":1779450453000},"source":"Crossref","is-referenced-by-count":0,"title":["The emerging roles of NFIL3 in immunity"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3240-0960","authenticated-orcid":false,"given":"Tomas Gregory","family":"Pepe","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, QC,","place":["Canada"]},{"name":"Victor Phillip Dahdaleh Institute of Genomic Medicine, McGill University , Montreal, QC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-0110","authenticated-orcid":false,"given":"David","family":"Langlais","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, QC,","place":["Canada"]},{"name":"Victor Phillip Dahdaleh Institute of Genomic Medicine, McGill University , Montreal, QC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2026052207453825900_vkag103-B1","doi-asserted-by":"crossref","first-page":"6055","DOI":"10.1128\/MCB.15.11.6055","article-title":"Molecular cloning and characterization of nf-il3a, a transcriptional activator of the human interleukin-3 promoter","volume":"15","author":"Zhang","year":"1995","journal-title":"Mol Cell 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