{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:31:12Z","timestamp":1792168272536,"version":"4.4.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2007,11,5]],"date-time":"2007-11-05T00:00:00Z","timestamp":1194220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Frequent injections of the hormonal form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D3 (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+\u2003forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2007.03537.x","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T21:15:40Z","timestamp":1280178940000},"page":"76-85","source":"Crossref","is-referenced-by-count":37,"title":["Comparative therapeutic effects of orally administered 1,25-dihydroxyvitamin D3 and 1alpha-hydroxyvitamin D3 on type-1 diabetes in non-obese diabetic mice fed a normal-calcaemic diet"],"prefix":"10.1093","volume":"151","author":[{"given":"J P","family":"Driver","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Foreman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology, Campus Gasthuisberg O&N1, Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Van Etten","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology, Campus Gasthuisberg O&N1, Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D V","family":"Serreze","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,11,5]]},"reference":[{"key":"2022010406281709900_b1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/9442","article-title":"The NOD mouse model of type 1 diabetes: as good as it gets?","volume":"5","author":"Atkinson","year":"1999","journal-title":"Nat Med"},{"key":"2022010406281709900_b2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.tem.2005.06.004","article-title":"Vitamin D and type 1 diabetes mellitus: state of the art","volume":"16","author":"Mathieu","year":"2005","journal-title":"Trends Endocrinol Metab"},{"key":"2022010406281709900_b3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1084\/jem.185.3.541","article-title":"Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative, but not positive selection of thymocytes in vivo","volume":"185","author":"Brocker","year":"1997","journal-title":"J Exp Med"},{"key":"2022010406281709900_b4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1084\/jem.186.2.239","article-title":"Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells","volume":"186","author":"Kurts","year":"1997","journal-title":"J Exp Med"},{"key":"2022010406281709900_b5","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.4049\/jimmunol.166.3.1439","article-title":"Dendritic cells are sufficient to cross-present self-antigens to CD8 T cells in vivo","volume":"166","author":"Kurts","year":"2001","journal-title":"J Immunol"},{"key":"2022010406281709900_b6","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1096\/fasebj.7.11.8370480","article-title":"Autoimmune diabetes results from genetic defects manifest by antigen presenting cells","volume":"7","author":"Serreze","year":"1993","journal-title":"FASEB"},{"key":"2022010406281709900_b7","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.4049\/jimmunol.162.3.1795","article-title":"Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells","volume":"162","author":"Delemarre","year":"1999","journal-title":"J Immunol"},{"key":"2022010406281709900_b8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0140-6736(95)90586-3","article-title":"Defective maturation and function of antigen-presenting cells in type 1 diabetes","volume":"345","author":"Jansen","year":"1995","journal-title":"Lancet"},{"key":"2022010406281709900_b9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1699-0463.1993.tb00126.x","article-title":"Defective HLA class II expression in monocytes of type 1 diabetic patients. 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