IgE actions on CD 4 + T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms

• Published in: EMBO molecular medicine Vol. 6; no. 7; pp. 952 - 969
• Main Authors: 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, Jian‐An, Shi, Guo‐Ping
• Format: Journal Article
• Language: English
• Published: Frankfurt EMBO Press 01.07.2014
• Subjects: Adoptive transfer; Angiotensin; Aortic aneurysms; Apolipoprotein E; Asthma; Atherosclerosis; CD4 antigen; CD8 antigen; Cytokines; Growth factors; Immunoglobulin E; Immunoglobulins; Inflammation; Interferon; Interleukin 1; Interleukin 10; Interleukin 6; Intravenous administration; Lymphocytes; Lymphocytes T; Macrophages; Mast cells; Monoclonal antibodies; Pathogenesis; Plasma; Proteins
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.201303811

Abstract 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. Synopsis image This study demonstrates the pathologic role of IgE and its high affinity receptor FcεR1 in AAA s by activating MC s, macrophages but also CD 4 and CD 8 T cells and suggests anti‐IgE antibodies as future putative therapeutics for treatment. IgE is expressed in MC s, macrophages, and CD 4 + and CD 8 + T cells in human AAA lesions. Genetic depletion of IgE high affinity receptor FcεR1 protects mice from AAA formation. Reduced AAA s in FcεR1‐deficient mice can be reversed to different extent after mice receiving donor MC s, macrophages, and CD 4 + T cells from wild‐type mice but not those from FcεR1‐deficient mice. Interruption of IgE‐FcεR1 interaction with an anti‐IgE antibody achieves similar AAA inhibitory effect to that from FcεR1‐deficient mice.