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Methimazole protects from experimental autoimmune uveitis (EAU) by inhibiting antigen presenting cell function and
Peng Wang1, Shu-Hui Sun, Phyllis B Silver
1Laboratory of Immunology, NEI/NIH, 10 Center Drive, Bethesda, MD 20892, USA.
Journal of Leukocyte Biology
|January 15, 2003
Summary
Methimazole (MMI) inhibits experimental autoimmune uveoretinitis (EAU) by impacting antigen-presenting cells during disease induction. This autoimmune disease treatment is effective early and independent of interferon-gamma signaling.
Area of Science:
- Immunology
- Ophthalmology
- Pharmacology
Background:
- Methimazole (MMI) is used for Graves' thyroiditis and shows promise in animal models of autoimmune diseases.
- Previous in vitro studies suggest MMI down-regulates interferon-gamma (IFN-γ)-induced MHC class I and II expression.
Purpose of the Study:
- To investigate the effect of MMI on experimental autoimmune uveoretinitis (EAU) and elucidate its underlying mechanisms.
- To determine if MMI's protective effects in EAU are IFN-γ-dependent.
Main Methods:
- MMI was administered in drinking water to EAU animal models.
- Flow cytometry was used to analyze draining lymph node cells (LNCs) for changes in antigen-presenting cell (APC) markers.
- Disease induction and antigen-specific T cell responses were assessed.
Main Results:
- MMI treatment inhibited EAU induction, antigen-specific proliferation, and cytokine production.
- MMI's protective effect was observed only when administered during the early phase of EAU induction.
- MMI inhibited EAU even in IFN-γ knockout mice, indicating an IFN-γ-independent mechanism.
- MMI treatment reduced the proportion of Mac-1, MHC class I/II, B7-1, and CD40-positive cells in draining LNCs, suggesting impaired APC function.
- Restoration of antigen-specific proliferation was observed when APC from untreated mice were added to MMI-treated LNCs.
Conclusions:
- MMI inhibits EAU induction, likely by interfering with the recruitment and/or maturation of antigen-presenting cells.
- This impairment of APC function leads to reduced generation of antigen-specific T cells, offering a novel therapeutic strategy for autoimmune uveitis.