{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:07:32Z","timestamp":1790633252536,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2001,11,1]],"date-time":"2001-11-01T00:00:00Z","timestamp":1004572800000},"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":[[2001,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immune cells carry receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; vitamin D receptor (VDR)] and individuals with severe vitamin D deficiency have immune abnormalities. The aim of this study was to investigate the role of vitamin D in the immune system by studying VDR-knockout (VDR-KO) mice. VDR-KO mice had the same metabolic phenotype as rachitic animals with severe hypocalcemia. Leukocytosis, lymphocyte subset composition in different immune organs, and splenocyte proliferation to several stimuli were normal, except for a lower response to anti-CD3 stimulation (simulation index [SI] of 13 \u00b1 4 vs. 24 \u00b1 9 in wild-type mice; p &amp;lt; 0.01). Macrophage chemotaxis was impaired (41 \u00b1 19% vs. 60 \u00b1 18% in wild-type mice; p &amp;lt; 0.01) but phagocytosis and killing were normal. In vivo rejection of allogeneic (31 \u00b1 12 days vs. 45 \u00b1 26 days of survival in wild-type mice, NS) or xenogeneic (10 \u00b1 2 days vs. 16 \u00b1 9 days of survival in wild-type mice, NS) islet grafts was comparable with wild-type mice. Surprisingly, VDR-KO mice were protected from low-dose streptozotocin-induced diabetes mellitus (LDSDM; 5% vs. 65% in wild-type mice; p &amp;lt; 0.001). Correcting hypocalcemia by use of lactose-rich or polyunsaturated fat-rich diets fully restored the immune abnormalities in vitro and the sensitivity to diabetes in vivo. On the other hand, treatment with 1,25(OH)2D3 protected wild-type mice against diabetes but did not protect normocalcemic VDR-KO mice. We conclude that immune defects observed in VDR-KO mice are an indirect consequence of VDR disruption because they can be restored by calcium homeostasis normalization. This study proves that although 1,25(OH)2D3 is a pharmacologic and probably a physiological immunomodulator, its immune function is redundant. Moreover, we confirm the essential role of calcium in the immune system.<\/jats:p>","DOI":"10.1359\/jbmr.2001.16.11.2057","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T03:34:56Z","timestamp":1146108896000},"page":"2057-2065","source":"Crossref","is-referenced-by-count":137,"title":["In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout Mice"],"prefix":"10.1093","volume":"16","author":[{"given":"Chantal","family":"Mathieu","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Van Etten","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny","family":"Gysemans","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Decallonne","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Laureys","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Leuven, 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