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

Jing Wang, Jes S. Lindholt, Galina K. Sukhova, Michael A. Shi, Mingcan Xia, Han Chen, Meixiang Xiang, Aina He, Yi Wang, Na Xiong, Peter Libby, Jian An Wang, Guo Ping Shi

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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.

Original languageEnglish (US)
Pages (from-to)952-969
Number of pages18
JournalEMBO Molecular Medicine
Volume6
Issue number7
DOIs
StatePublished - Jul 2014

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine

Cite this

Wang, J., Lindholt, J. S., Sukhova, G. K., Shi, M. A., Xia, M., Chen, H., Xiang, M., He, A., Wang, Y., Xiong, N., Libby, P., Wang, J. A., & Shi, G. P. (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. https://doi.org/10.15252/emmm.201303811