Open AccessIgE actions on CD 4 + T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms
Author(s) -
Wang Jing,
Lindholt Jes S,
Sukhova Galina K,
Shi Michael A,
Xia Mingcan,
Chen Han,
Xiang Meixiang,
He Aina,
Wang Yi,
Xiong Na,
Libby Peter,
Wang JianAn,
Shi GuoPing
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201303811
Subject(s) - immunoglobulin e , pathogenesis , immunology , apolipoprotein e , antibody , adoptive cell transfer , chemistry , medicine , microbiology and biotechnology , t cell , biology , immune system , pathology , disease
Immunoglobulin E (IgE) activates mast cells ( MC s). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms ( AAA s). This study demonstrates that CD 4 + T cells express IgE receptor FcεR1, at much higher levels than do CD 8 + T cells. IgE induces CD 4 + T‐cell production of IL 6 and IFN ‐γ, but reduces their production of IL 10. FcεR1 deficiency ( Fcer1a −/− ) protects apolipoprotein E‐deficient ( Apoe −/− ) mice from angiotensin‐ II infusion‐induced AAA s and reduces plasma IL 6 levels. Adoptive transfer of CD 4 + T cells (but not CD 8 + T cells), MC s, and macrophages from Apoe −/− mice, but not those from Apoe −/− Fcer1a −/− mice, increases AAA size and plasma IL 6 in Apoe −/− Fcer1a −/− recipient mice. Biweekly intravenous administration of an anti‐IgE monoclonal antibody ablated plasma IgE and reduced AAA s in Apoe −/− mice. Patients with AAA s had significantly higher plasma IgE levels than those without AAA s. This study establishes an important role of IgE in AAA pathogenesis by activating CD 4 + T cells, MC s, and macrophages and supports consideration of neutralizing plasma IgE in the therapeutics of human AAA s.