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Med."},{"key":"10.1016\/j.omta.2026.201817_bib75","doi-asserted-by":"crossref","DOI":"10.1002\/cpz1.1092","article-title":"Update: Induction of Inflammatory Bowel Disease in Immunodeficient Mice by Injection of Na\u00efve CD4+ T cells (T Cell Transfer Model of Colitis)","volume":"4","author":"Pearson","year":"2024","journal-title":"Curr. Protoc."},{"key":"10.1016\/j.omta.2026.201817_bib76","doi-asserted-by":"crossref","first-page":"G135","DOI":"10.1152\/ajpgi.90462.2008","article-title":"T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade","volume":"296","author":"Ostanin","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. 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Interferon Cytokine Res."},{"key":"10.1016\/j.omta.2026.201817_bib89","doi-asserted-by":"crossref","DOI":"10.3390\/biom12091282","article-title":"DNA Methylation in Regulatory T Cell Differentiation and Function: Challenges and Opportunities","volume":"12","author":"Bai","year":"2022","journal-title":"Biomolecules"},{"key":"10.1016\/j.omta.2026.201817_bib90","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0001612","article-title":"FOXP3 promoter demethylation reveals the committed Treg population in humans","volume":"3","author":"Janson","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.omta.2026.201817_bib91","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1084\/jem.20070109","article-title":"CREB\/ATF-dependent T cell receptor\u2013induced FoxP3 gene expression: a role for DNA methylation","volume":"204","author":"Kim","year":"2007","journal-title":"J. Exp. 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