Establishment of Nasal Tolerance to Heat Shock Protein-60 Alleviates Atherosclerosis by Inducing TGF-β-dependent Regulatory T Cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2012-02, Vol.32 (1), p.24-30
• Main Author: 李海禹 丁艳萍 易桂文 曾秋棠 杨文凯
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Antibodies; Aorta; Apolipoprotein E; Arteriosclerosis; Atherogenesis; Atherosclerosis - immunology; Atherosclerosis - pathology; Atherosclerosis - prevention & control; atherosclerosis; inflammation; immune; CD25 antigen; CD4 antigen; cells; Chaperonin 60 - administration & dosage; Chaperonin 60 - immunology; Cytokines; Foxp3 protein; Heat shock; Hsp60 protein; Immune Tolerance - drug effects; Immune Tolerance - immunology; Immunological tolerance; Immunoregulation; Inflammation; Intranasal administration; Lymphocytes T; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phosphate; protein; regulatory; shock; T-Lymphocytes, Regulatory - immunology; tolerance; heat; Transforming Growth Factor beta - immunology; Transforming growth factor- beta; Treatment Outcome
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-012-0004-z

Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.