{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:34:29Z","timestamp":1791016469350,"version":"4.1.0"},"reference-count":6,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,11,9]],"date-time":"2006-11-09T00:00:00Z","timestamp":1163030400000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Increasing attention is drawn to the contributions of abnormalities in both innate and acquired immune responses to the pathogenesis of autoimmune diseases, such as type 1 diabetes (T1D). Dendritic cells (DC) are critical immune cells linking innate and acquired immune responses and previous studies in NOD mice suggest abnormalities in these cells.<\/jats:bold>\n          <jats:bold>To address DC dysregulation we examined kinetic global gene expression in NOD and B6 GM\u2010CSF\/IL\u20104\u2010induced bone marrow\u2010derived DC following lipopolysaccharide (LPS)\u2010stimulation. We identified expression differences in over 300 genes including a cluster of 16 interferon (IFN\u2010\u03b1\/\u03b2) target genes overexpressed in NOD DC. Mechanistically, heightened IFN\u2010\u03b1\/\u03b2 responses were not due to increased production of this cytokine, IFN\u2010\u03b3 priming or increased Syk kinase activity. We found, however, heightened responses to IFN\u2010\u03b1\/\u03b2 in NOD versus B6 as demonstrated by increased type 1 IFN target gene expression, for example, IRF\u20107, in NOD DC and macrophages. Analysis of multiple congenic strains demonstrated that the <jats:italic>Idd5<\/jats:italic> susceptibility region largely governed heightened IFN\u2010\u03b1 responses. Of interest, heightened IFN\u2010\u03b1\/\u03b2 response in NOD mice was not confined to hematopoietic cells but was also seen in the pancreas and \u03b2 cells. Compounding the IFN\u2010\u03b1 response defect, NOD mice harbor significantly more PDC in spleen in comparison to B6 and produce four\u2010 to sixfold more IFN\u2010\u03b1 when stimulated with CpG. Finally, treatment of NOD mice with IFN\u2010\u03b1 inducing agents, for example, high\u2010dose poly I:C accelerates diabetes in both female and male mice. The abnormalities in the IFN\u2010\u03b1\/\u03b2 axis appear to play a significant role in T1D pathogenesis.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1375.013","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T03:23:30Z","timestamp":1164684210000},"page":"99-102","source":"Crossref","is-referenced-by-count":12,"title":["Heightened Interferon\u2010\u03b1\/\u03b2 Response Causes Myeloid Cell Dysfunction and Promotes T1D Pathogenesis in NOD Mice"],"prefix":"10.1111","volume":"1079","author":[{"given":"RUI HUA","family":"PENG","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EDWARD","family":"PAEK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHANQING Q.","family":"XIA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NATHAN","family":"TENNYSON","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MICHAEL J.","family":"CLARE\u2010SALZLER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,9]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.9.3263"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.4.1947"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5748"},{"key":"e_1_2_5_5_2","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2337\/diab.44.6.658","article-title":"Stewart interferon expression in the pancreases of patients with type I diabetes","volume":"44","author":"Huang X.","year":"1995","journal-title":"Diabetes"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03464"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041930"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1375.013","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1375.013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T08:55:31Z","timestamp":1695632131000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1375.013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10]]},"references-count":6,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["10.1196\/annals.1375.013"],"URL":"https:\/\/doi.org\/10.1196\/annals.1375.013","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10]]}}}