PMID- 32844222
OWN - NLM
STAT- MEDLINE
DCOM- 20210301
LR  - 20210301
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 12
DP  - 2020 Dec 1
TI  - Vitamin D Supplementation Modulates ICOS+ and ICOS- Regulatory T Cell in Siblings 
      of Children With Type 1 Diabetes.
LID - dgaa588 [pii]
LID - 10.1210/clinem/dgaa588 [doi]
AB  - 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 <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 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Savastio, Silvia
AU  - Savastio S
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
FAU - Cadario, Francesco
AU  - Cadario F
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
AD  - Interdisciplinary Research Center of Autoimmune Diseases, Universita del Piemonte 
      Orientale, Novara, Italy.
FAU - D'Alfonso, Sandra
AU  - D'Alfonso S
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Stracuzzi, Marta
AU  - Stracuzzi M
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
FAU - Pozzi, Erica
AU  - Pozzi E
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
FAU - Raviolo, Silvia
AU  - Raviolo S
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
FAU - Rizzollo, Stefano
AU  - Rizzollo S
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
FAU - Gigliotti, Luca
AU  - Gigliotti L
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Boggio, Elena
AU  - Boggio E
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Bellomo, Giorgio
AU  - Bellomo G
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Basagni, Chiara
AU  - Basagni C
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Bona, Gianni
AU  - Bona G
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Rabbone, Ivana
AU  - Rabbone I
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
FAU - Dianzani, Umberto
AU  - Dianzani U
AD  - Interdisciplinary Research Center of Autoimmune Diseases, Universita del Piemonte 
      Orientale, Novara, Italy.
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
AD  - SCDU of Clinical Biochemistry, University Hospital Maggiore della Carita, Novara, 
      Italy.
FAU - Prodam, Flavia
AU  - Prodam F
AD  - SCDU of Pediatrics, University Hospital Maggiore della Carita, Novara, Italy.
AD  - Interdisciplinary Research Center of Autoimmune Diseases, Universita del Piemonte 
      Orientale, Novara, Italy.
AD  - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (ICOS protein, human)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
RN  - 1406-16-2 (Vitamin D)
SB  - IM
MH  - Child
MH  - *Diabetes Mellitus, Type 1
MH  - Dietary Supplements
MH  - Female
MH  - Humans
MH  - Inducible T-Cell Co-Stimulator Protein/*metabolism
MH  - Italy/epidemiology
MH  - Lymphocyte Count
MH  - Male
MH  - *Siblings
MH  - T-Lymphocytes, Regulatory/*drug effects/metabolism/pathology
MH  - Th17 Cells/cytology/drug effects/metabolism
MH  - Vitamin D/administration & dosage/*pharmacology
MH  - *Vitamin D Deficiency/drug therapy/epidemiology/immunology/metabolism
OTO - NOTNLM
OT  - Th 17
OT  - Treg
OT  - Type 1 diabetes
OT  - immunomodulation
OT  - vitamin D
EDAT- 2020/08/28 06:00
MHDA- 2021/03/02 06:00
CRDT- 2020/08/27 06:00
PHST- 2020/04/21 00:00 [received]
PHST- 2020/08/21 00:00 [accepted]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2021/03/02 06:00 [medline]
PHST- 2020/08/27 06:00 [entrez]
AID - 5897243 [pii]
AID - 10.1210/clinem/dgaa588 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa588. doi: 10.1210/clinem/dgaa588.