Vitamin D Supplementation Modulates ICOS+ and ICOS− Regulatory T Cell in Siblings of Children With Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2020-12, Vol.105 (12), p.e4767-e4777
• Main Authors: Savastio, Silvia, Cadario, Francesco, D’Alfonso, Sandra, Stracuzzi, Marta, Pozzi, Erica, Raviolo, Silvia, Rizzollo, Stefano, Gigliotti, Luca, Boggio, Elena, Bellomo, Giorgio, Basagni, Chiara, Bona, Gianni, Rabbone, Ivana, Dianzani, Umberto, Prodam, Flavia
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D; Autoimmunity; CCR6 protein; CD25 antigen; CD4 antigen; Child; Children; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1; Dietary Supplements; Female; Foxp3 protein; Haplotypes; Helper cells; Hemoglobin; Histocompatibility antigen HLA; Humans; Immunoregulation; Inducible T-Cell Co-Stimulator Protein - metabolism; Italy - epidemiology; Lymphocyte Count; Lymphocytes T; Male; Siblings; Supplements; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Th17 Cells - cytology; Th17 Cells - drug effects; Th17 Cells - metabolism; Vitamin D; Vitamin D - administration & dosage; Vitamin D - pharmacology; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - epidemiology; Vitamin D Deficiency - immunology; Vitamin D Deficiency - metabolism; Vitamin deficiency
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa588

Abstract Objectives 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. Patients and Methods 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 “at risk” (HLA+), “protective haplotypes” (HLA−; “nested controls”), and “undetermined” (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU/die and evaluated after 6 months. Results Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels 75 nmol/L. Treg/ICOS+ percentages (P < 0.05) were higher in HLA− 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 < 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 < 0.0001), and lower Th17 (P < 0.0001) and Treg/ICOS+ (P < 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P < 0.05). Conclusion 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.