Published online before print September 9, 2009

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0409231

Received for publication April 6, 2009.
Revised July 31, 2009.
Accepted for publication August 7, 2009.

Article

IgE signaling suppresses FcRI expression

Jennifer Brenzovich ^*, Matthew Macey ^*, Josephine Fernando ^*, Hey Jin Chong ^*, Brian Barnstein ^*, Paria Mirmonsef ^*, Johanna K. Morales ^*, Akiko Kimura , Tracey Dawson Cruz ^* , and John J. Ryan ^*@

Departments of *Biology andForensic Science, Virginia Commonwealth University, Richmond, Virginia, USA; andNational Institute of Diabetes, Digestive, and Kidney Disorders, National Institutes of Health, Bethesda, Maryland, USA

^@ To whom correspondence should be addressed. E-mail: jjryan{at}vcu.edu.

Abstract

Activation of the high-affinity receptor for IgE, FcRI, is known to elicit its rapid down-regulation through internalization and degradation. In keeping with this, expression of all three FcRI subunits is decreased at the protein level after cross-linkage of IgE with antigen. However, we find that the FcRI -subunit is also selectively suppressed at the mRNA level, through a pathway primarily involving Fyn, Syk, PI3K, and NF-B. IgG or calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade, similarly suppressed -subunit expression. LPS, a NF-B-activating TLR ligand, did not alter -subunit expression. As IgE increases FcRI expression, we examined the coordinated regulation of FcRI subunits during culture with IgE, followed by cross-linkage with antigen. IgE increased the expression of all three FcRI subunits and strikingly induced expression of the antagonistic _T. The ratio of :_T 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 and _T mRNAs. FcRI is a key regulator of IgER expression and function, a gene in which polymorphisms correlate with allergic disease prevalence. The ability of IgE and FcRI signaling to coordinate expression of the and _T subunits may comprise a homeostatic feedback loop—one that could promote chronic inflammation and allergic disease if dysregulated.

Key Words: mast cells • allergy • FcRI • -chain • IgE