In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 86, No. 6 ( 2009-09-09), p. 1351-1358
Abstract:
The IgE receptor regulates its own expression partly by altering the levels of its b and bT subunits and this antagonistic pair determines the extent to which mast cells are activated in allergic disease. Activation of the high-affinity receptor for IgE, FcεRI, is known to elicit its rapid down-regulation through internalization and degradation. In keeping with this, expression of all three FcεRI subunits is decreased at the protein level after cross-linkage of IgE with antigen. However, we find that the FcεRI β-subunit is also selectively suppressed at the mRNA level, through a pathway primarily involving Fyn, Syk, PI3K, and NF-κB. IgG or calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade, similarly suppressed β-subunit expression. LPS, a NF-κB-activating TLR ligand, did not alter β-subunit expression. As IgE increases FcεRI expression, we examined the coordinated regulation of FcεRI subunits during culture with IgE, followed by cross-linkage with antigen. IgE increased the expression of all three FcεRI subunits and strikingly induced expression of the antagonistic βT. The ratio of β:βT protein expression decreased significantly during culture with IgE and was reset to starting levels by antigen cross-linkage. These changes in protein levels were matched by similar fluctuations in β and βT mRNAs. FcεRIβ is a key regulator of IgER expression and function, a gene in which polymorphisms correlate with allergic disease prevalence. The ability of IgE and FcεRI signaling to coordinate expression of the β and βT subunits may comprise a homeostatic feedback loop—one that could promote chronic inflammation and allergic disease if dysregulated.
Type of Medium:
Online Resource
ISSN:
1938-3673
,
0741-5400
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2009
detail.hit.zdb_id:
2026833-6
SSG:
12
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