{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T03:57:17Z","timestamp":1772078237669,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["26460572"],"award-info":[{"award-number":["26460572"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>An age-dependent increase in interferon (IFN)-\u03b3 expression by intestinal intraepithelial lymphocytes (IELs) contributes to the acquisition of resistance to infection by pathogens. However, how IELs acquire the ability to produce IFN-\u03b3 remains to be elucidated. Here, we report that IELs in the small intestine acquire the ability to rapidly produce IFN-\u03b3 at two distinct life stages. TCR\u03b1\u03b2+ IELs (\u03b1\u03b2IELs) started producing IFN-\u03b3 at 4 weeks of age, within 1 week after weaning. In contrast, TCR\u03b3\u03b4+ IELs (\u03b3\u03b4IELs) started producing IFN-\u03b3 at 7 weeks of age. In mice lacking E\u03b34, an enhancer of the TCR\u03b3 locus (E\u03b34\u2212\/\u2212 mice), Thy-1+ V\u03b35+ \u03b3\u03b4IELs, a major subpopulation of \u03b3\u03b4IELs, were specifically reduced and their ability to produce IFN-\u03b3 was severely impaired, whereas V\u03b32+ \u03b3\u03b4IELs normally produced IFN-\u03b3. In E\u03b34\u2212\/\u2212 mice, TCR expression levels were reduced in V\u03b35+ \u03b3\u03b4IEL precursors in the thymus but unchanged in the V\u03b35+ IELs. Nevertheless, TCR responsiveness in V\u03b35+ \u03b3\u03b4IELs was impaired in E\u03b34\u2212\/\u2212 mice, suggesting that the TCR signal received in the thymus may determine TCR responsiveness and the ability to produce IFN-\u03b3 in the gut. These results suggest that \u03b1\u03b2IELs and \u03b3\u03b4IELs start producing IFN-\u03b3 at different life stages and that the ability of V\u03b35+ \u03b3\u03b4IELs to produce IFN-\u03b3 in the gut may be predetermined by TCR signalling in IEL precursors in the thymus.<\/jats:p>","DOI":"10.1093\/intimm\/dxae034","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T22:59:04Z","timestamp":1717541944000},"page":"653-661","source":"Crossref","is-referenced-by-count":1,"title":["\u03b3\u03b4 intraepithelial lymphocytes acquire the ability to produce IFN-\u03b3 in a different time course than \u03b1\u03b2 intraepithelial lymphocytes"],"prefix":"10.1093","volume":"36","author":[{"given":"Shizue","family":"Tani-ichi","sequence":"first","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,","place":["Japan"]},{"name":"Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1319-1021","authenticated-orcid":false,"given":"Koichi","family":"Ikuta","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University , Kyoto ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"2024112205261508200_CIT0001","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.it.2017.11.003","article-title":"Intestinal intraepithelial lymphocytes: sentinels of the mucosal barrier","volume":"39","author":"Olivares-Villagomez","year":"2018","journal-title":"Trends Immunol"},{"key":"2024112205261508200_CIT0002","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1093\/intimm\/7.9.1473","article-title":"Intra-epithelial lymphocytes. 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