The western-type diet induces anti-HMGB1 autoimmunity in Apoe(-/-) mice.
Atherosclerosis
; 251: 31-38, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27240253
ABSTRACT
BACKGROUND AND AIMS:
Anti-HMGB1 autoimmunity plays a role in systemic lupus erythematosus (SLE). Because SLE increases atherosclerosis, we asked whether the same autoimmunity might play a role in atherogenesis.METHODS:
We looked for the induction of HMGB1-specific B and T cell responses by a western-type diet (WTD) in the Apoe(-/-) mouse model of atherosclerosis. We also determined whether modifying the responses modulates atherosclerosis.RESULTS:
In the plasma of male Apoe(-/-) mice fed WTD, the level of anti-HMGB1 antibodies (Abs) was detected at â¼50 µg/ml, which was â¼6 times higher than that in either Apoe(-/-) mice fed a normal chow or Apoe(+/+) mice fed WTD (p ≤ 0.0005). The Abs were directed largely toward a novel, dominant epitope of HMGB1 named HMW4; accordingly, compared with chow-fed mice, WTD-fed Apoe(-/-) mice had more activated HMW4-reactive B and T cells (p = 0.005 and p = 0.01, respectively). Compared with mock-immunized mice, Apoe(-/-) mice immunized with HMW4 along with an immunogenic adjuvant showed proportional increases in anti-HMW4 IgG and IgM Abs, HMW4-reactive B-1 and B-2 cells, and HMW4-reactive Treg and Teff cells, which was associated with â¼30% increase in aortic arch lesions (p ≤ 0.01) by two methods. In contrast, Apoe(-/-) mice immunized with HMW4 using a tolerogenic adjuvant showed preferential increases in anti-HMW4 IgM (over IgG) Abs, HMW4-reactive B-1 (over B-2) cells, and HMW4-specific Treg (over Teff) cells, which was associated with â¼40% decrease in aortic arch lesions (p ≤ 0.03).CONCLUSIONS:
Anti-HMGB1 autoimmunity may potentially play a role in atherogenesis.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
/
Proteína HMGB1
/
Aterosclerose
/
Dieta Ocidental
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos