{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T22:29:43Z","timestamp":1787264983650,"version":"build-2736575974"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001364","name":"University of Florida Foundation","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100001364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK94244"],"award-info":[{"award-number":["DK94244"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:p>\n                    Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation. Elevated fecal lipocalin-2, calprotectin, IgG levels, and dysbiosis support the inflammatory phenotype. Here, we show through RNA-sequencing, using purified intestinal epithelial cells (IECs), that\n                    <jats:italic>Zip14<\/jats:italic>\n                    deletion produces markedly reduced expression of major histocompatibility complex class II (MHCII) molecules and the master MHCII transactivator (\n                    <jats:italic>Ciita<\/jats:italic>\n                    ). qPCR, western analysis, and immunohistochemistry confirmed loss of MHCII. Spectrofluorimetry with zinc probe FluoZin-3 showed reduced labile zinc in IECs from knockout mice. Chromatin immunoprecipitation assays, using Ciita antibody and IEC chromatin, suggest decreased transcription accounts for depressed expression of specific MHCII genes. Assay for Transposase-Accessible Chromatin (ATAC) sequencing (ATAC-seq) demonstrated that\n                    <jats:italic>H2-Aa<\/jats:italic>\n                    ,\n                    <jats:italic>H2-Ab1<\/jats:italic>\n                    and other MHCII genes result from chromatin remodeling yielding closed chromatin at regulatory regions of these genes. In agreement, ATAC-seq showed peak density of the chromosomal regulatory region of Ciita is consistent with down regulation of specific MHCII genes in IECs with\n                    <jats:italic>Zip14<\/jats:italic>\n                    loss. Finally, dietary zinc supplementation of knockout mice and zinc supplementation of intestinal organoids with\n                    <jats:italic>Zip14<\/jats:italic>\n                    deletion restored transcript levels. Taken together, our data suggest that cellular zinc delivery, via Zip14, is necessary for proper chromatin occupancy, required for normal MHCII expression and effective immune functions, and to preclude inflammatory disorders of the small intestine.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2422321121","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T15:00:46Z","timestamp":1735570846000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells"],"prefix":"10.1073","volume":"122","author":[{"given":"Felix R.","family":"Jimenez-Rondan","sequence":"first","affiliation":[{"name":"Center for Nutritional Sciences, Food Science and Human Nutrition Department","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney H.","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Center for Nutritional Sciences, Food Science and Human Nutrition Department","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Riva","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, Interdisciplinary Center for Biotechnology Research","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahong","family":"Yu","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, Interdisciplinary Center for Biotechnology Research","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S.","family":"Stafford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler R.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Joseph","family":"Larkin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-7827","authenticated-orcid":false,"given":"Robert J.","family":"Cousins","sequence":"additional","affiliation":[{"name":"Center for Nutritional Sciences, Food Science and Human Nutrition Department","place":["Gainesville"]},{"name":"College of Agricultural and Life Sciences","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]},{"name":"Department of Biochemistry and Molecular Biology","place":["Gainesville"]},{"name":"College of Medicine","place":["Gainesville"]},{"name":"University of Florida","place":["Gainesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2024.100181"},{"key":"e_1_3_4_2_2","volume-title":"The Double Burden of Malnutrition: Policy Brief","author":"Organization W. 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