title: Establishment of nasal tolerance to heat shock protein-60 alleviates atherosclerosis by inducing TGF-β-dependent regulatory T cells.
abstract: 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 administered 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 compared with those in the PBS-treated mice. Atherosclerosis suppression was accompanied with a significant 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-β antibody. 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.
authors.affiliation: Institute of Cardiology, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Cardiology, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Cardiology, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Guiwen
authors.initials: G
authors.lastname: Yi
authors.affiliation: Institute of Cardiology, Huazhong University of Science and Technology, Wuhan, 430022, China. zqtdoctor@yahoo.cn.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Cardiac Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Yang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018834:Chaperonin 60 / Q000008:administration & dosage* / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D018834:Chaperonin 60; D016212:Transforming Growth Factor beta