Vitamin D Supplementation modulates ICOS+ and ICOS- regulatory T cell in siblings of Children with Type 1 Diabetes.

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/ICOS + which seems to have a protective role in autoimmunity, in children with 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, HbA1c, 25(OH)D, Th17 (CD4 +CCR6 +), Treg (CD4 +CD25 +Foxp3 +), and Treg/ICOS + cells were evaluated. According to HLA haplotypes, subjects were classified as "at risk" (HLA +), "protective haplotypes" (HLA -; "nested controls"), and "undetermined" (HLA UND). T1D and S subjects were supplemented with cholecalciferol 1,000 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 &25 nmol/L had Th17, Treg (p&0.01) and Treg/ICOS + (p&0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS + percentages (p&0.05) were higher in HLA - S subjects compared to percentages observed in their siblings 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 + (R-square: 0.301) and Th17 percentages (R-square: 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.