title: The western-type diet induces anti-HMGB1 autoimmunity in Apoe(-/-) mice.
abstract: 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.
  
  
  
  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.
  
  
  
  In the plasma of male Apoe(-/-) mice fed WTD, the level of anti-HMGB1 antibodies (Abs) was detected at ∼50 μg/ml, which was ∼6 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 ∼30% 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 ∼40% decrease in aortic arch lesions (p ≤ 0.03).
  
  
  
  Anti-HMGB1 autoimmunity may potentially play a role in atherogenesis.
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Ke
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Asner
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Palani
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Gnanasekar
authors.initials: G
authors.lastname: Munirathinam
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Subramanyam
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Karin C
authors.initials: KC
authors.lastname: Nitiss
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bliss
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA.
authors.forename: Hongming
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pathology (C.A.R., G.S.G.), University of Chicago, Chicago, IL 60637, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
authors.affiliation: Department of Pathology (C.A.R., G.S.G.), University of Chicago, Chicago, IL 60637, USA.
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA. Electronic address: aoshuang@uic.edu.
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107, USA. Electronic address: guoxingz@uic.edu.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000941:Antigens / Q000097:blood; D001013:Aorta, Thoracic / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D066273:Diet, Western / Q000009:adverse effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D024243:HMGB1 Protein / Q000235:genetics*; D007249:Inflammation; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE
chemical_list: D000941:Antigens; D000939:Epitopes; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008055:Lipids
keywords: Anti-HMGB1 autoimmunity; Apoe(−/−) mice; Atherosclerosis; Western-type diet