{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T01:11:50Z","timestamp":1778461910784,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,2,26]],"date-time":"2008-02-26T00:00:00Z","timestamp":1203984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007229","name":"Harvard University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Developmental biology has long been ignored in the etiology and diverse manifestations of autoimmune diseases. Yet a role for development is suggested by intriguing overlaps in particular organs targeted in autoimmune diseases, in this case type 1 diabetes and Sjogren's syndrome. Patients with type 1 diabetes have high rates of co\u2010occurring Sjogren's syndrome, and both conditions are associated with hearing loss and tongue abnormalities. All of these co\u2010occurrences are found in organs tracing their lineage to the developmental transcription factor <jats:italic>Hox11<\/jats:italic>, which is expressed in embryonic cells destined for the pancreas, salivary glands, tongue, cranial nerves and cochlea. To determine whether development contributes to autoimmunity, we compared four target organs in NOD mice (an animal model for type 1 diabetes and Sjogren's syndrome) with NOD\u2010SCID mice (which lack lymphocytes) and normal controls. We examined the structure and\/or function of the cochlea, salivary glands, pancreas and tongue at early time points after birth. Before the usual time of the onset of type 1 diabetes or Sjogren's syndrome, we show that all four <jats:italic>Hox11<\/jats:italic>\u2010derived organs are structurally abnormal in both NOD mice and NOD\u2010SCID mice versus controls. The most striking functional defect is near complete hearing loss occurring before the normal time of the onset of autoimmunity. The hearing loss is associated with severe structural defects in the cochlea, suggesting that near\u2010deafness occurs independent of autoimmune attack. The pancreas and salivary glands are also structurally abnormal in NOD and NOD\u2010SCID mice, but they are functionally normal. This suggests that autoimmune attack of these two organs is required for functional failure. We conclude that a developmental lineage of cells contributes to autoimmunity and predicts which organs may be targeted, either structurally and\/or functionally. Taken together, our findings challenge the orthodoxy that autoimmunity is solely caused by a defective immune system.<\/jats:p>","DOI":"10.1038\/icb.2008.6","type":"journal-article","created":{"date-parts":[[2008,2,26]],"date-time":"2008-02-26T14:34:20Z","timestamp":1204036460000},"page":"301-309","source":"Crossref","is-referenced-by-count":16,"title":["Fetal <i>Hox11<\/i> expression patterns predict defective target organs: a novel link between developmental biology and autoimmunity"],"prefix":"10.1111","volume":"86","author":[{"given":"Anna","family":"Lonyai","sequence":"first","affiliation":[{"name":"Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School Charlestown MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohta","family":"Kodama","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Burger","sequence":"additional","affiliation":[{"name":"Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School Charlestown MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise L","family":"Faustman","sequence":"additional","affiliation":[{"name":"Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School Charlestown MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,2,26]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402214"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780080"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0050"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.038"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-200304000-00009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/95.2.79"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1995.0009"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-003-1053-9"},{"key":"e_1_2_7_9_1","first-page":"151","article-title":"Autoantibodies and autoimmune diseases in young diabetics","volume":"13","author":"Kontiainen S","year":"1990","journal-title":"Diabetes Res"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2000.15.3.202"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.1996.9.S1.89"},{"issue":"1","key":"e_1_2_7_12_1","first-page":"597","article-title":"Celiac disease and its link to type 1 diabetes mellitus","volume":"14","author":"Schuppan D","year":"2001","journal-title":"J Pediatr Endocrinol Metab"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199802)15:2<148::AID-DIA540>3.0.CO;2-H"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000023344"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/28.6.518"},{"key":"e_1_2_7_16_1","first-page":"798","article-title":"How significant is sensorineural hearing loss in primary Sjogren's syndrome? 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