A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice

Silvia Gregori, Nadia Giarratana, Simona Smiroldo, Milan Uskokovic, Luciano Adorini

Research output: Contribution to journalArticle

381 Citations (Scopus)

Abstract

Type 1 diabetes is a chronic progressive autoimmune disease characterized by mononuclear cell infiltration, dominated by interleukin-12 (IL-12)-dependent Th1 cells, of the pancreatic islets, with subsequent destruction of insulin-producing β-cells. Here, we demonstrate that treatment of adult nonobese diabetic (NOD) mice with an analog of 1α,25-dihydroxyvitamin D3, an immunomodulatory agent preventing dendritic cell maturation, decreases lipopolysaccharide-induced IL-12 and γ-interferon production, arrests Th1 cell infiltration and progression of insulitis, and inhibits diabetes development at nonhypercalcemic doses. Arrest of disease progression is accompanied by an enhanced frequency in the pancreatic lymph nodes of CD4+CD25+ regulatory T-cells that are able to inhibit the T-cell response to the pancreatic autoantigen insulinoma-associated protein 2 and to significantly delay disease transfer by pathogenic CD4+CD25- cells. Thus, a short treatment of adult NOD mice with an analog of 1,25-dihydroxy-vitamin D3 inhibits IL-12 production, blocks pancreatic infiltration of Th1 cells, enhances CD4+CD25+ regulatory cells, and arrests the progression of type 1 diabetes, suggesting its possible application in the treatment of human autoimmune diabetes.

Original languageEnglish
Pages (from-to)1367-1374
Number of pages8
JournalDiabetes
Volume51
Issue number5
Publication statusPublished - 2002

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Inbred NOD Mouse
Calcitriol
Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Th1 Cells
Interleukin-12
Class 8 Receptor-Like Protein Tyrosine Phosphatases
Islets of Langerhans
Dendritic Cells
Interferons
Autoimmune Diseases
Lipopolysaccharides
Disease Progression
Lymph Nodes
Insulin
T-Lymphocytes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Gregori, S., Giarratana, N., Smiroldo, S., Uskokovic, M., & Adorini, L. (2002). A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes, 51(5), 1367-1374.

A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. / Gregori, Silvia; Giarratana, Nadia; Smiroldo, Simona; Uskokovic, Milan; Adorini, Luciano.

In: Diabetes, Vol. 51, No. 5, 2002, p. 1367-1374.

Research output: Contribution to journalArticle

Gregori, S, Giarratana, N, Smiroldo, S, Uskokovic, M & Adorini, L 2002, 'A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice', Diabetes, vol. 51, no. 5, pp. 1367-1374.
Gregori, Silvia ; Giarratana, Nadia ; Smiroldo, Simona ; Uskokovic, Milan ; Adorini, Luciano. / A 1α,25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. In: Diabetes. 2002 ; Vol. 51, No. 5. pp. 1367-1374.
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