{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:59:27Z","timestamp":1777478367803,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1\u03b1-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus. Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1. Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell\u2013specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.<\/jats:p>","DOI":"10.4049\/jimmunol.1602080","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T20:50:13Z","timestamp":1510001413000},"page":"3952-3958","source":"Crossref","is-referenced-by-count":13,"title":["Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice"],"prefix":"10.1093","volume":"199","author":[{"given":"Juliane","family":"Lindner","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Rausch","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie-Fachbereich Veterin\u00e4rmedizin, Freie Universit\u00e4t , D-14163 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Treptow","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Geldmeyer-Hilt","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Krause","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"St-Arnaud","sequence":"additional","affiliation":[{"name":"Research Centre, Shriners Hospitals for Children-Canada , Montreal, Quebec H4A 0A9,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Arabian","sequence":"additional","affiliation":[{"name":"Research Centre, Shriners Hospitals for Children-Canada , Montreal, Quebec H4A 0A9,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Radbruch","sequence":"additional","affiliation":[{"name":"Deutsches Rheuma-Forschungszentrum , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie-Fachbereich Veterin\u00e4rmedizin, Freie Universit\u00e4t , D-14163 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3449-1245","authenticated-orcid":false,"given":"Margitta","family":"Worm","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-9862","authenticated-orcid":false,"given":"Guido","family":"Heine","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charit\u00e9, Campus Charit\u00e9 Mitte, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , D-10117 Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"2025030614543233200_r1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ncpendmet0716","article-title":"Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity","volume":"4","author":"Adams","year":"2008","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"2025030614543233200_r2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1126\/science.6310748","article-title":"1,25-dihydroxyvitamin D3 receptors in human leukocytes","volume":"221","author":"Provvedini","year":"1983","journal-title":"Science"},{"key":"2025030614543233200_r3","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.4049\/jimmunol.157.7.2900","article-title":"Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes","volume":"157","author":"Morgan","year":"1996","journal-title":"J. Immunol."},{"key":"2025030614543233200_r4","first-page":"3395","article-title":"1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro","volume":"32","author":"Heine","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"2025030614543233200_r5","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.jaci.2010.08.020","article-title":"Vitamin D receptor binds to the epsilon germline gene promoter and exhibits transrepressive activity","volume":"126","author":"Milovanovic","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030614543233200_r6","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1398-9995.2010.02513.x","article-title":"Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response","volume":"66","author":"Hartmann","year":"2011","journal-title":"Allergy"},{"key":"2025030614543233200_r7","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.4049\/jimmunol.173.5.3432","article-title":"Vitamin D receptor-deficient mice fail to develop experimental allergic asthma","volume":"173","author":"Wittke","year":"2004","journal-title":"J. Immunol."},{"key":"2025030614543233200_r8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/ni1433","article-title":"DCs metabolize sunlight-induced vitamin D3 to \u2018program\u2019 T cell attraction to the epidermal chemokine CCL27","volume":"8","author":"Sigmundsdottir","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025030614543233200_r9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/exd.12300","article-title":"Oral vitamin D increases the frequencies of CD38+ human B cells and ameliorates IL-17-producing T cells","volume":"23","author":"Drozdenko","year":"2014","journal-title":"Exp. Dermatol."},{"key":"2025030614543233200_r10","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1002\/eji.200838216","article-title":"1,25-dihydroxyvitamin D(3) promotes IL-10 production in human B cells","volume":"38","author":"Heine","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2025030614543233200_r11","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/j.1398-9995.2008.01865.x","article-title":"Serum 25-hydroxyvitamin D and IgE - a significant but nonlinear relationship","volume":"64","author":"Hypp\u00f6nen","year":"2009","journal-title":"Allergy"},{"key":"2025030614543233200_r12","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1164\/rccm.200808-1361OC","article-title":"Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica","volume":"179","author":"Brehm","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025030614543233200_r13","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.4049\/jimmunol.1301656","article-title":"25-hydroxvitamin D3 promotes the long-term effect of specific immunotherapy in a murine allergy model","volume":"193","author":"Heine","year":"2014","journal-title":"J. Immunol."},{"key":"2025030614543233200_r14","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1210\/endo.142.7.8281","article-title":"Targeted inactivation of the 25-hydroxyvitamin D(3)-1(alpha)-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets","volume":"142","author":"Dardenne","year":"2001","journal-title":"Endocrinology"},{"key":"2025030614543233200_r15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jsbmb.2004.03.113","article-title":"Mice lacking 25OHD 1alpha-hydroxylase demonstrate decreased epidermal differentiation and barrier function","volume":"89\u201390","author":"Bikle","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2025030614543233200_r16","doi-asserted-by":"crossref","first-page":"13789","DOI":"10.1073\/pnas.0605944103","article-title":"Testing gene function early in the B cell lineage in mb1-cre mice","volume":"103","author":"Hobeika","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614543233200_r17","first-page":"93","article-title":"Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages\/neutrophils: protective and deleterious effects","volume":"22","author":"Grivennikov","year":"2005","journal-title":"Immunity"},{"key":"2025030614543233200_r18","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1182\/blood-2012-03-414821","article-title":"Biphenotypic B-lymphoid\/myeloid cells expressing low levels of Pax5: potential targets of BAL development","volume":"120","author":"Simmons","year":"2012","journal-title":"Blood"},{"key":"2025030614543233200_r19","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.4049\/jimmunol.0801804","article-title":"Liver X receptors control IgE expression in B cells","volume":"182","author":"Heine","year":"2009","journal-title":"J. Immunol."},{"key":"2025030614543233200_r20","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1038\/jid.2008.84","article-title":"Systemic PPARgamma ligation inhibits allergic immune response in the skin","volume":"128","author":"Dahten","year":"2008","journal-title":"J. Invest. Dermatol."},{"key":"2025030614543233200_r21","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-3024.2006.00891.x","article-title":"Screening for immunomodulatory proteins of the intestinal parasitic nematode Heligmosomoides polygyrus","volume":"28","author":"Rzepecka","year":"2006","journal-title":"Parasite Immunol."},{"key":"2025030614543233200_r22","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1111\/exd.12261","article-title":"Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen-induced eczema model","volume":"22","author":"Mudnakudu Nagaraju","year":"2013","journal-title":"Exp. Dermatol."},{"key":"2025030614543233200_r23","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nri1886","article-title":"Competence and competition: the challenge of becoming a long-lived plasma cell","volume":"6","author":"Radbruch","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"2025030614543233200_r24","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.jaci.2009.06.047","article-title":"Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge","volume":"124","author":"Luger","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030614543233200_r25","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nri1181","article-title":"The regulation of immunoglobulin E class-switch recombination","volume":"3","author":"Geha","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025030614543233200_r26","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1038\/jid.2010.175","article-title":"Interleukin-17A promotes IgE production in human B cells","volume":"130","author":"Milovanovic","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"2025030614543233200_r27","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.bbrc.2011.03.078","article-title":"1,25-dihydroxyvitamin D3 impairs NF-\u03baB activation in human na\u00efve B cells","volume":"407","author":"Geldmeyer-Hilt","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025030614543233200_r28","doi-asserted-by":"crossref","first-page":"13968","DOI":"10.1073\/pnas.0906367106","article-title":"Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function","volume":"106","author":"Massacand","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614543233200_r29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/jid.2012.239","article-title":"TSLP produced by keratinocytes promotes allergen sensitization through skin and thereby triggers atopic march in mice","volume":"133","author":"Leyva-Castillo","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"2025030614543233200_r30","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1056\/NEJMcpc049016","article-title":"Case records of the Massachusetts general hospital. Weekly clinicopathological exercises. Laboratory reference values","volume":"351","author":"Kratz","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"2025030614543233200_r31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1365-2265.2011.04261.x","article-title":"An update on vitamin D and human immunity","volume":"76","author":"Hewison","year":"2012","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"2025030614543233200_r32","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nri2378","article-title":"Vitamin effects on the immune system: vitamins A and D take centre stage","volume":"8","author":"Mora","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025030614543233200_r33","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.4049\/jimmunol.1601213","article-title":"Control of circulating IgE by the vitamin D receptor in vivo involves B cell intrinsic and extrinsic mechanisms","volume":"198","author":"James","year":"2017","journal-title":"J. Immunol."},{"key":"2025030614543233200_r34","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.4049\/jimmunol.0804344","article-title":"TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses","volume":"182","author":"Enioutina","year":"2009","journal-title":"J. Immunol."},{"key":"2025030614543233200_r35","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.4049\/jimmunol.179.3.1634","article-title":"Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation","volume":"179","author":"Chen","year":"2007","journal-title":"J. Immunol."},{"key":"2025030614543233200_r36","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S8756-3282(03)00023-1","article-title":"Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1)","volume":"32","author":"Dardenne","year":"2003","journal-title":"Bone"},{"key":"2025030614543233200_r37","doi-asserted-by":"crossref","first-page":"7498","DOI":"10.1073\/pnas.131029498","article-title":"Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction","volume":"98","author":"Panda","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614543233200_r38","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1749-6632.2003.tb06057.x","article-title":"Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting autoimmune diabetes","volume":"987","author":"Adorini","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025030614543233200_r39","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.4049\/jimmunol.164.5.2405","article-title":"1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation","volume":"164","author":"Penna","year":"2000","journal-title":"J. Immunol."},{"key":"2025030614543233200_r40","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1084\/jem.20011629","article-title":"In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines","volume":"195","author":"Barrat","year":"2002","journal-title":"J. Exp. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/12\/3952\/61532603\/ji1602080.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/12\/3952\/61532603\/ji1602080.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T16:57:07Z","timestamp":1741280227000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/199\/12\/3952\/7966130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":40,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1602080","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,12]]},"published":{"date-parts":[[2017,12]]}}}