{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:44:41Z","timestamp":1791081881754,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T00:00:00Z","timestamp":1297728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Surgery and the Department of Medicine, University of Illinois at Chicago"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p>Epigenetic alteration of the genome has been shown to provide palliative effects in mouse models of certain human autoimmune diseases. We have investigated whether chromatin remodeling could provide protection against autoimmune diabetes in NOD mice. Treatment of female mice during the transition from prediabetic to diabetic stage (18\u201324 weeks of age) with the well\u2010characterized histone deacetylase inhibitor, trichostatin A effectively reduced the incidence of diabetes. However, similar treatment of overtly diabetic mice during the same time period failed to reverse the disease. Protection against diabetes was accompanied by histone hyperacetylation in pancreas and spleen, enhanced frequency of CD4<jats:sup>+<\/jats:sup> CD62L<jats:sup>+<\/jats:sup> cells in the spleen, reduction in cellular infiltration of islets, restoration of normoglycemia and glucose\u2010induced insulin release by beta cells. Activation of splenic T lymphocytes derived from protected mice <jats:italic>in vitro<\/jats:italic> with pharmacological agents that bypass the antigen receptor or immobilized anti\u2010CD3 antibody resulted in enhanced expression of <jats:italic>Ifng<\/jats:italic> mRNA and protein without altering the expression of <jats:italic>Il4<\/jats:italic>, <jats:italic>Il17<\/jats:italic>, <jats:italic>Il18<\/jats:italic>, <jats:italic>Inos<\/jats:italic> and <jats:italic>Tnfa<\/jats:italic> genes nor the secretion of IL\u20102, IL\u20104, IL\u201017 and TNF\u2010\u03b1 proteins. Consistently, expression of the transcription factor involved in <jats:italic>Ifng<\/jats:italic> transcription, <jats:italic>Tbet\/Tbx21<\/jats:italic> but not <jats:italic>Gata3<\/jats:italic> and <jats:italic>Rorgt,<\/jats:italic> respectively, required for the transcription of <jats:italic>Il4<\/jats:italic> and <jats:italic>Il17,<\/jats:italic> was upregulated in activated splenocytes of protected mice. These results indicate that chromatin remodeling can lead to amelioration of diabetes by using multiple mechanisms including differential gene transcription. Thus, epigenetic modulation could be a novel therapeutic approach to block the transition from benign to frank diabetes.<\/jats:p>","DOI":"10.1038\/icb.2010.144","type":"journal-article","created":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T16:59:41Z","timestamp":1297789181000},"page":"640-649","source":"Crossref","is-referenced-by-count":54,"title":["Chromatin remodeling resets the immune system to protect against autoimmune diabetes in mice"],"prefix":"10.1111","volume":"89","author":[{"given":"Tejas","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Surgery, College of Medicine, University of Illinois at Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasu","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, University of Illinois at Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajvir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, University of Illinois at Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundararajan","family":"Jayaraman","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, University of Illinois at Chicago  Chicago IL USA"},{"name":"Department of Medicine, College of Medicine, University of Illinois at Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063127"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200111000-00010"},{"key":"e_1_2_7_3_1","first-page":"245","article-title":"The expression of a small fraction of cellular genes is changed in response to histone hyeracetylation","volume":"5","author":"Van Lint C","year":"1996","journal-title":"Gene Expr"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-3-30"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.49.453"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16153"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2073"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051507098"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1652"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2008.04.020"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.5015"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.02006.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.02.022"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.08.002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2260"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2636971100"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916939309043886"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1113"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.5865"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-8411(91)90021-4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115055"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5491"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.995"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2008.11.029"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.S114"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065543"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1762"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.035"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903615"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.6964"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.6.812"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.12.8940385"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13844"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.12.2007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3919"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.2002.0604"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh173"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071878"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0360328"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1332767100"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.6.3457"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804154"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1288.024"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03059.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.1.44"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.04.004"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00413-08"},{"key":"e_1_2_7_50_1","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.4049\/jimmunol.148.9.2672","article-title":"Tolerance induction in T helper (Th1) cells by thymic macrophages","volume":"148","author":"Jayaraman S","year":"1992","journal-title":"J Immunol"}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Ficb.2010.144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/icb.2010.144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1038\/icb.2010.144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/icb.2010.144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:28:09Z","timestamp":1694021289000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1038\/icb.2010.144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,15]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1038\/icb.2010.144"],"URL":"https:\/\/doi.org\/10.1038\/icb.2010.144","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,15]]}}}