IgE actions on CD 4 + T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms
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 lev...
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Published in | EMBO molecular medicine Vol. 6; no. 7; pp. 952 - 969 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frankfurt
EMBO Press
01.07.2014
|
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 1757-4676 1757-4684 |
DOI: | 10.15252/emmm.201303811 |