IgE actions on CD 4 + 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 FceR1, at much higher levels than do CD8 T cells. IgE induces CD4 T-cell production of IL6 and IFN-c, but reduces their production of IL10. FceR1 deficiency (Fcer1a / ) protects apolipoprotein E-deficient (Apoe / ) mice from angiotensin-II infusioninduced 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.