{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:13:24Z","timestamp":1791209604422,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,24]]},"abstract":"<jats:p>\n                    Feedback regulation of transcription factor NF-\u03baB by its inhibitor I\u03baB\u03b1 plays an essential role in control of NF-\u03baB activity. To understand the biological significance of I\u03baB\u03b1-mediated feedback regulation of NF-\u03baB, we generated mice harboring mutated \u03baB enhancers in the promoter of the\n                    <jats:italic>I\u03baB\u03b1<\/jats:italic>\n                    gene (\n                    <jats:italic>\n                      I\u03baB\u03b1\n                      <jats:sup>M\/M<\/jats:sup>\n                    <\/jats:italic>\n                    ) to inhibit NF-\u03baB\u2013regulated I\u03baB\u03b1 expression. Here, we report that these mutant mice are defective in NF-\u03baB\u2013induced expression of I\u03baB\u03b1. This defective feedback regulation of NF-\u03baB by I\u03baB\u03b1 not only altered activity of NF-\u03baB, but also the expression of NF-\u03baB\u2013regulated genes. As a result,\n                    <jats:italic>\n                      I\u03baB\u03b1\n                      <jats:sup>M\/M<\/jats:sup>\n                    <\/jats:italic>\n                    , the homozygous knock-in mice with mutated \u03baB enhancers in the\n                    <jats:italic>I\u03baB\u03b1<\/jats:italic>\n                    promoter, acquire shorten life span, hypersensitivity to septic shock, abnormal T-cell development and activation, and Sj\u00f6gren\n                    <jats:italic>\u2019<\/jats:italic>\n                    s Syndrome. These findings therefore demonstrate that the I\u03baB\u03b1-mediated feedback regulation of NF-\u03baB has an essential role in controlling T-cell development and functions, provide mechanistic insight into the development of Sj\u00f6gren\n                    <jats:italic>\u2019<\/jats:italic>\n                    s Syndrome, and suggest the potential of NF-\u03baB signaling as a therapeutic target for Sj\u00f6gren\n                    <jats:italic>\u2019<\/jats:italic>\n                    s Syndrome and other autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1005533107","type":"journal-article","created":{"date-parts":[[2010,8,9]],"date-time":"2010-08-09T23:08:03Z","timestamp":1281395283000},"page":"15193-15198","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Defective feedback regulation of NF-\u03baB underlies Sj\u00f6gren\n                    <i>\u2019<\/i>\n                    s syndrome in mice with mutated \u03baB enhancers of the\n                    <i>I\u03baB\u03b1<\/i>\n                    promoter"],"prefix":"10.1073","volume":"107","author":[{"given":"Bailu","family":"Peng","sequence":"first","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Ling","sequence":"additional","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Joon","family":"Lee","sequence":"additional","affiliation":[{"name":"Pennsylvania State University College of Medicine, Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilai","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics and"},{"name":"Neuroscience and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chang","sequence":"additional","affiliation":[{"name":"University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030; Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[{"name":"Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya'an","family":"Kang","sequence":"additional","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Shim","sequence":"additional","affiliation":[{"name":"Neuroscience and"},{"name":"The Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamin","family":"Wang","sequence":"additional","affiliation":[{"name":"Pathology, and"},{"name":"University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030; Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason B.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics and"},{"name":"Neuroscience and"},{"name":"The Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Cong","family":"Sun","sequence":"additional","affiliation":[{"name":"Immunology,"},{"name":"University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030; Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Chiao","sequence":"additional","affiliation":[{"name":"Departments of aSurgical Oncology\u2013Research,"},{"name":"Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;"},{"name":"University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030; Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1422.046"},{"key":"e_1_3_3_2_2","first-page":"E325","article-title":"Sj\u00f6gren's syndrome of the oral cavity. Review and update","volume":"14","author":"Margaix-Mu\u00f1oz M","year":"2009","unstructured":"M Margaix-Mu\u00f1oz, JV Bag\u00e1n, R Poveda, Y Jim\u00e9nez, G Sarri\u00f3n, Sj\u00f6gren's syndrome of the oral cavity. Review and update. 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