title: IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms.
abstract: Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD8+ T cells. IgE induces CD4+ T-cell production of IL6 and IFN-γ, but reduces their production of IL10. FcεR1 deficiency (Fcer1a-/-) protects apolipoprotein E-deficient (Apoe-/-) mice from angiotensin-II infusion-induced AAAs and reduces plasma IL6 levels. Adoptive transfer of CD4+ T cells (but not CD8+ T cells), MCs, and macrophages from Apoe-/- mice, but not those from Apoe-/- Fcer1a-/- mice, increases AAA size and plasma IL6 in Apoe-/- Fcer1a-/- recipient mice. Biweekly intravenous administration of an anti-IgE monoclonal antibody ablated plasma IgE and reduced AAAs in Apoe-/- mice. Patients with AAAs had significantly higher plasma IgE levels than those without AAAs. This study establishes an important role of IgE in AAA pathogenesis by activating CD4+ T cells, MCs, and macrophages and supports consideration of neutralizing plasma IgE in the therapeutics of human AAAs.
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Jing
authors: J
authors: Wang
authors: Department of Cardiovascular and Thoracic Surgery, Elitary Research Centre of Individualized Medicine in Arterial Diseases, University Hospital of Odense, Odense, Denmark.
authors: Jes S
authors: JS
authors: Lindholt
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Galina K
authors: GK
authors: Sukhova
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Michael A
authors: MA
authors: Shi
authors: Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA.
authors: Mingcan
authors: M
authors: Xia
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, College of Medicine, The Second Affiliated Hospital Zhejiang University, Hangzhou, China.
authors: Han
authors: H
authors: Chen
authors: Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, College of Medicine, The Second Affiliated Hospital Zhejiang University, Hangzhou, China.
authors: Meixiang
authors: M
authors: Xiang
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Aina
authors: A
authors: He
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Yi
authors: Y
authors: Wang
authors: Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA.
authors: Na
authors: N
authors: Xiong
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Peter
authors: P
authors: Libby
authors: Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, College of Medicine, The Second Affiliated Hospital Zhejiang University, Hangzhou, China gshi@rics.bwh.harvard.edu wja@zju.edu.cn.
authors: Jian-An
authors: JA
authors: Wang
authors: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA gshi@rics.bwh.harvard.edu wja@zju.edu.cn.
authors: Guo-Ping
authors: GP
authors: Shi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
chemical_list: D017455:Receptors, IgE; D007073:Immunoglobulin E
keywords: IgE; T cells; abdominal aortic aneurysm; macrophage; mast cell