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International Immunology Advance Access originally published online on June 8, 2005
International Immunology 2005 17(6):685-694; doi:10.1093/intimm/dxh248
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Role of the Fc{epsilon}RI ß-chain ITAM as a signal regulator for mast cell activation with monomeric IgE

Satoshi Nunomura1, Yasuhiro Gon1,2, Tetsuro Yoshimaru1, Yoshihiro Suzuki1, Hajime Nishimoto3, Toshiaki Kawakami3 and Chisei Ra1

1 Division of Molecular Cell Immunology and Allergology and
2 First Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan
3 Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive San Diego, CA 92121, USA

Correspondence to: C. Ra; E-mail: fcericra{at}med.nihon-u.ac.jp

The ß-chain of the high-affinity receptor for IgE (Fc{epsilon}RI) plays a crucial role for amplification of the intracellular signaling in mast cells upon Fc{epsilon}RI cross-linking by IgE•antigen complexes (IgE•Ag). Some monomeric IgE as well as IgE•Ag stimulate Fc{epsilon}RI-signaling pathways, leading to cell activation, whereas the biological functions of the ß-chain in the monomeric IgE-mediated mast cell signaling and responses are largely unknown. In the present study, Fc{epsilon}RI is reconstituted with either wild-type ß-chain or mutated ß-chain immunoreceptor tyrosine-based activation motif (ITAM) employing retrovirus-mediated gene transfer into the Fc{epsilon}RI ß-chain–/– mast cells. We demonstrated that the transfectants with mutated ß-chain ITAM stimulated with monomeric IgE sufficiently produce inflammatory cytokines, although degranulation, intracellular Ca2+ mobilization and leukotriene C4 synthesis are significantly reduced. Furthermore, analyses of molecular mechanisms of the signaling revealed that the expression of cytokine genes and activation of extracellular signal-regulated kinase 1/2 and protein kinase C were significantly delayed in the ß-chain ITAM mutant cells stimulated with monomeric IgE, suggesting that the ß-chain ITAM regulates kinetics of gene transcriptions and signaling pathways for cytokine production. These findings for the first time revealed the unique functions of the ß-chain ITAM in both chemical mediator release and cytokine production of mast cells upon monomeric IgE stimulation.

Keywords: allergy, Fc receptors, mast cells, signal transduction

Transmitting editor: H. Karasuyama


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