IgE actions on CD4(+) T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms

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.