Published online before print September 9, 2009

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(Journal of Leukocyte Biology. 2009;86:1351-1358.)
© 2009 Society for Leukocyte Biology

IgE signaling suppresses FcRIβ 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^*,1

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

1. Correspondence: Virginia Commonwealth University, Biology Department, Box 842012, Richmond, VA 23284-2012, USA. 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 β-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 β-subunit expression. LPS, a NF-B-activating TLR ligand, did not alter β-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 β_T. The ratio of β:β_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 β and β_T mRNAs. FcRIβ 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 β and β_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 • β-chain • IgE