{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:18:34Z","timestamp":1779920314591,"version":"3.53.1"},"reference-count":82,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2017-0535"],"award-info":[{"award-number":["2017-0535"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg\/inducible costimulatory-positive (ICOS+), which seems to have a protective role in autoimmunity, in children with type 1 diabetes mellitus (T1D) and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>22 T1D and 33 S were enrolled. Glucose, hemoglobin A1c, 25 OH vitamin D (25[OH]D), T helper type 17 (Th17; CD4+CCR6+), regulatory T cells (Treg; CD4+CD25+Foxp3+), and Treg\/ICOS+ cells were evaluated. According to human leukocyte antigen (HLA) haplotypes, subjects were classified as \u201cat risk\u201d (HLA+), \u201cprotective haplotypes\u201d (HLA\u2212; \u201cnested controls\u201d), and \u201cundetermined\u201d (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU\/die and evaluated after 6 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels &amp;lt;25 nmol\/L had Th17, Treg (p &amp;lt; 0.01), and Treg\/ICOS+ (P &amp;lt; 0.05) percentages higher than subjects with 25(OH)D &amp;gt;75 nmol\/L. Treg\/ICOS+ percentages (P &amp;lt; 0.05) were higher in HLA\u2212 S subjects compared to percentages observed in S with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg\/ICOS+ values (P &amp;lt; 0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg\/ICOS+ (R2 = 0.301) and Th17 percentages (R2 = 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (P &amp;lt; 0.0001), and lower Th17 (P &amp;lt; 0.0001) and Treg\/ICOS+ (P &amp;lt; 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P &amp;lt; 0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa588","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T05:57:10Z","timestamp":1598421430000},"page":"e4767-e4777","source":"Crossref","is-referenced-by-count":14,"title":["Vitamin D Supplementation Modulates ICOS+ and ICOS\u2212 Regulatory T Cell in Siblings of Children With Type 1 Diabetes"],"prefix":"10.1210","volume":"105","author":[{"given":"Silvia","family":"Savastio","sequence":"first","affiliation":[{"name":"SCDU of Pediatrics, University Hospital Maggiore della Carit\u00e0, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cadario","sequence":"additional","affiliation":[{"name":"SCDU of Pediatrics, University Hospital Maggiore della Carit\u00e0, Novara, Italy"},{"name":"Interdisciplinary Research Center of Autoimmune Diseases, Universit\u00e0 del Piemonte Orientale, 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