{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:38:38Z","timestamp":1789925918729,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010215","name":"Deutsche Diabetes Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010215","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Autoimmune polyglandular syndrome (APS-2: autoimmune Addison\u2019s disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      APS-2 patients (n = 30) and healthy controls (n = 30) were genotyped for HLA DQA1\/DQB1 and their CD14+ monocytes stimulated with IL1\u03b2 and\/or 1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      for 24\u00a0h. Immune regulatory molecules (IL-6, IL-10, IL-23A, IL-15, CCL-2, PD-L1), vitamin D pathway gene transcripts (CYP24A1, CYP27B1, VDR), and CD14 were analyzed by enzyme-linked immunosorbent assay and RTqPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pro-inflammatory CCL-2 was higher in APS-2 patients than in controls (p\u00a0= 0.001), whereas IL-6 showed a trend \u2013 (p = 0.1). In vitro treatment with 1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      reduced proinflammatory cytokines (IL-6, CCL-2, IL-23A, IL-15) whereas anti-inflammatory cytokines (IL-10 and PD-L1) rose both in APS-type 1 diabetes and APS-Addison\u00b4s disease. Patients with adrenal autoimmunity showed a stronger response to vitamin\u00a0D. Expression of IL-23A and vitamin D pathway genes VDR and CYP27B1 varied by HLA genotype and was lower in healthy individuals with high-risk HLA (p = 0.0025; p = 0.04), while healthy controls with low-risk HLA showed a stronger IL-10 and CD14 expression (p = 0.01; p = 0.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      regulates the monocytic response in APS-2 disorders type 1 diabetes or Addison\u00b4s disease. The monocytic cytokine profile of individuals carrying HLA high-risk alleles is proinflammatory, enhances polyglandular autoimmunity and can be targeted by vitamin D.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2020.583709","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:23:11Z","timestamp":1607300591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin\u00a0D and HLA-DQ"],"prefix":"10.3389","volume":"11","author":[{"given":"Anna U.","family":"Kraus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Penna-Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firouzeh","family":"Shoghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Badenhoop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06580-1","article-title":"Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study","volume":"358","author":"Hypp\u00f6nen","year":"2001","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01211.x","article-title":"Vitamin D and increasing incidence of type 1 diabetes-evidence for an association","volume":"12","author":"Hypp\u00f6nen","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092185","article-title":"Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes","volume":"11","author":"Infante","year":"2019","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s40519-016-0312-6","article-title":"Vitamin D: not just the bone. 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