Retinoids differentially regulate the progression of autoimmune diabetes in three preclinical models in mice

Stanislava Stosić-Grujicić1, Tamara Cvjetićanin, Ivana Stojanović

  • 1Department of Immunology, Institute for Biological Research Sinisa Stanković, Belgrade University, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. duta@eunet.rs

Molecular Immunology
|February 13, 2009
PubMed

Insights

Retinoids like etretinate and all-trans-retinoic acid (ATRA) show promise in preventing type 1 diabetes (T1D) by modulating immune responses. Their effectiveness in preclinical models depends on the presence of regulatory T cells (Tregs).

Area of Science:

  • Immunology
  • Endocrinology
  • Pharmacology

Background:

  • Retinoids possess immunomodulatory properties relevant to inflammatory and autoimmune diseases.
  • Type 1 diabetes (T1D) involves complex autoimmune pathogenesis.
  • Understanding T1D's immune triggers is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the potential of retinoids, specifically etretinate and all-trans-retinoic acid (ATRA), in preclinical models of T1D.
  • To elucidate the mechanisms underlying retinoid-mediated prevention of T1D.
  • To determine the role of regulatory T cells (Tregs) in retinoid efficacy for T1D.

Main Methods:

  • Prophylactic administration of etretinate and ATRA to streptozotocin-induced diabetic CBA/H mice.
  • Assessment of clinical diabetes signs, immune cell populations (CD4+CD25+ T cells, Foxp3+ Tregs), and cytokine profiles (Th1/Th17, NO).
  • Treatment of non-obese diabetic (NOD) mice with ATRA before T1D onset, including experiments with cyclophosphamide (CY)-induced Treg abrogation.

Main Results:

  • Both etretinate and ATRA prevented clinical T1D in MLD-STZ treated mice.
  • T1D prevention was linked to reduced autoreactive T cells but not increased Tregs.
  • ATRA treatment decreased Th1/Th17 responses and nitric oxide (NO) production.
  • ATRA prophylaxis reduced hyperglycemia and T1D incidence in spontaneous NOD mouse models.
  • ATRA's protective effect was lost when Tregs were abrogated by CY.

Conclusions:

  • Retinoids, including ATRA, can effectively prevent T1D in preclinical models.
  • The immunomodulatory effects of retinoids involve suppressing inflammatory responses and shifting cytokine balance.
  • The therapeutic efficacy of retinoids in T1D is dependent on the presence and function of regulatory T cells (Tregs).

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