IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms
Lindholt, Jes S
Shi, Michael A
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CitationWang, J., J. S. Lindholt, G. K. Sukhova, M. A. Shi, M. Xia, H. Chen, M. Xiang, et al. 2014. “IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms.” EMBO Molecular Medicine 6 (7): 952-969. doi:10.15252/emmm.201303811. http://dx.doi.org/10.15252/emmm.201303811.
AbstractImmunoglobulin 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.
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