Induction of immune tolerance in mice with a novel mucosal nanoemulsion adjuvant and self-antigen

Nanomedicine (Lond). 2012 Jun;7(6):867-76. doi: 10.2217/nnm.11.187. Epub 2012 Mar 15.

Abstract

Aim: The aim of this study was to investigate the impact of a novel nanoemulsion (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in mice as a study model.

Materials & methods: Mice received NE or NE + mTg by nasal delivery. At 1 week after the second nasal delivery of NE with or without mTg, all mice were immunized with mTg and lipopolysaccharides to induce experimental autoimmune thyroiditis.

Results: Compared with controls, mTg-NE-treated mice had much more antigens accumulated in the nasal passage and thymus and developed a milder form of thyroiditis. This was accompanied by an increase in IL-10, IL-17 and reduced IFN-γ. The production of anti-mTg antibodies was significantly decreased in mTg-NE-treated mice. The percentage of Tregs in cervical lymph nodes was higher in mTg-NE-treated mice than NE-treated mice. Furthermore, Foxp3 and TGF-β levels were prominently enhanced in mTg-NE-treated mice.

Conclusion: This study indicates that a low dose of mTg in NE can significantly enhance antigen uptake and Tregs, resulting in inhibition of experimental autoimmune thyroiditis development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Administration, Intranasal
  • Animals
  • Autoantibodies / immunology
  • Emulsions / administration & dosage
  • Emulsions / therapeutic use*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Immune Tolerance*
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred CBA
  • RNA, Messenger / genetics
  • Soybean Oil / administration & dosage
  • Soybean Oil / immunology
  • Soybean Oil / therapeutic use*
  • T-Lymphocytes, Regulatory / immunology
  • Thyroglobulin / administration & dosage*
  • Thyroglobulin / immunology*
  • Thyroid Gland / immunology
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / pathology
  • Thyroiditis, Autoimmune / prevention & control*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology

Substances

  • Adjuvants, Immunologic
  • Autoantibodies
  • Emulsions
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • RNA, Messenger
  • Transforming Growth Factor beta
  • anti-thyroglobulin
  • Interleukin-10
  • Soybean Oil
  • Interferon-gamma
  • Thyroglobulin