{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:57:11Z","timestamp":1790092631594,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"publisher","award":["JP18K07170"],"award-info":[{"award-number":["JP18K07170"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"publisher","award":["JP22K08795"],"award-info":[{"award-number":["JP22K08795"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD8\u03b1\u03b1+ intestinal intraepithelial lymphocytes (iIELs) are known for their unique role in keeping the integrity of the intestinal epithelial barrier, but factors affecting the development of these cells have not been thoroughly understood. Here, we found that the transcriptional regulator interferon regulatory factor-2 (IRF-2) plays a cell-intrinsic, indispensable role in establishing iIEL populations. CD8\u03b1\u03b1+, but not CD8\u03b1\u03b2+, iIELs bearing TCR\u03b1\u03b2 or TCR\u03b3\u03b4 were severely reduced in numbers in mice lacking this factor (Irf2\u2013\/\u2013 mice). Moreover, the majority of residual CD8\u03b1\u03b1+TCR\u03b1\u03b2+ iIELs in these mice was immature as judged from their Thy1.2high phenotype and inefficient T-bet expression. Thymic IEL precursors isolated from Irf2\u2013\/\u2013 mice failed to efficiently generate CD8\u03b1\u03b1+TCR\u03b1\u03b2+ and TCR\u03b3\u03b4+ IELs upon transfer in vivo and CD8\u03b1\u03b1+TCR\u03b1\u03b2+ cells in response to IL-15 in vitro. Double mutant mice lacking both interleukin-15 (IL-15) and IRF-2 showed an even more severe iIEL defect than in mice lacking IL-15 alone. Upon increasing agonistic TCR signal strength through OT-II TCR transgenesis, CD8\u03b1\u03b1+TCR\u03b1\u03b2+ iIELs became more abundant but remained immature on the Irf2\u2013\/\u2013 background. Our current observations, thus, revealed the unique bimodal role that IRF-2 plays in promoting not only generation of IEL progenitors in the thymus but also maturation of iIELs in the periphery in IL-15-dependent and -independent manners.<\/jats:p>","DOI":"10.1093\/intimm\/dxac058","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T23:20:47Z","timestamp":1671146447000},"page":"231-241","source":"Crossref","is-referenced-by-count":2,"title":["Interferon regulatory factor-2 is required for the establishment of the gut intraepithelial T-cell compartment"],"prefix":"10.1093","volume":"35","author":[{"given":"Shigeo","family":"Tokumaru","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Immunology, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"},{"name":"Department of Surgery, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Immunology, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"},{"name":"Department of Surgery, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Immunology, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"},{"name":"Department of Surgery, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Soejima","sequence":"additional","affiliation":[{"name":"Department of Surgery, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Sanjo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Immunology, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-3496","authenticated-orcid":false,"given":"Shinsuke","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Immunology, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"2023050806120147900_CIT0001","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. 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