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Oral dosing with multi-antigenic construct induces atheroprotective immune tolerance to individual peptides in mice.

Abstract：

:Inflammatory immune response to self-antigens plays an important role in the development of atherosclerosis. Restoring immune tolerance to self-proteins reduces the pro-inflammatory response. We previously showed that oral tolerance to a combination of two peptides is atheroprotective. In the present study we expressed epitopes from apolipoprotein B 100 (ApoB), human heat shock protein (HSP60) and Chlamydia pneumonia outer membrane protein (Cpn) in a single protein scaffold and used this multi-antigenic construct to induce tolerance to individual peptides by oral route in ApoBtm2Sgy/Ldlrtm1Her/J mice. Antigen specific tolerance to individual peptides was observed in treated animals as seen by an increase in regulatory T cells. Tolerance to the peptides resulted in a 46.5% (p=0.002) reduction in the development of atherosclerosis compared with control. Atheroprotection was associated with a significant (p<0.05) decrease in plaque inflammation and an increase in the expression of immune regulatory markers in the aorta. CD11c+ cells coexpressing CD11b and CD103 increased in lymphoid organs and were found to activate regulatory T cells and reduce effector T-cell response. Adoptive transfer of CD11c+ cells was atheroprotective. Our results suggest that atheroprotection by oral tolerance to a multi-antigenic construct is mediated by antigen specific regulatory T cells and CD11c+ cells with immune regulatory properties.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Mundkur L,Ponnusamy T,Philip S,Rao LN,Biradar S,Deshpande V,Kumar R,Lu X,Kakkar VV

doi

10.1016/j.ijcard.2014.06.001

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

340-51

issue

2

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(14)01064-X

journal_volume

175

pub_type

杂志文章

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