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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftE M B O Molecular Medicine (Online)
Vol/bind6
Udgave nummer7
Sider (fra-til)952-69
Antal sider18
ISSN1757-4676
DOI
StatusUdgivet - jul. 2014

Fingeraftryk

Abdominal Aortic Aneurysm
Mast Cells
Macrophages
Interleukin-6
IgE Receptors
Interleukin-10

Citer dette

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. / IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms. I: E M B O Molecular Medicine (Online). 2014 ; Bind 6, Nr. 7. s. 952-69.
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title = "IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms",
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.",
author = "Jing Wang and Lindholt, {Jes S} and Sukhova, {Galina K} and Shi, {Michael A} and Mingcan Xia and Han Chen and Meixiang Xiang and Aina He and Yi Wang and Na Xiong and Peter Libby and Jian-An Wang and Guo-Ping Shi",
note = "{\circledC} 2014 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2014",
month = "7",
doi = "10.15252/emmm.201303811",
language = "English",
volume = "6",
pages = "952--69",
journal = "E M B O Molecular Medicine (Online)",
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Wang, J, Lindholt, JS, Sukhova, GK, Shi, MA, 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', E M B O Molecular Medicine (Online), bind 6, nr. 7, s. 952-69. https://doi.org/10.15252/emmm.201303811

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

I: E M B O Molecular Medicine (Online), Bind 6, Nr. 7, 07.2014, s. 952-69.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms

AU - Wang, Jing

AU - Lindholt, Jes S

AU - Sukhova, Galina K

AU - Shi, Michael A

AU - Xia, Mingcan

AU - Chen, Han

AU - Xiang, Meixiang

AU - He, Aina

AU - Wang, Yi

AU - Xiong, Na

AU - Libby, Peter

AU - Wang, Jian-An

AU - Shi, Guo-Ping

N1 - © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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.

U2 - 10.15252/emmm.201303811

DO - 10.15252/emmm.201303811

M3 - Journal article

VL - 6

SP - 952

EP - 969

JO - E M B O Molecular Medicine (Online)

JF - E M B O Molecular Medicine (Online)

SN - 1757-4676

IS - 7

ER -