AUTHOR=Ra Chisei , Nunomura Satoshi , Okayama Yoshimichi 

TITLE=Fine-tuning of mast cell activation by FceRIbeta chain

JOURNAL=Frontiers in Immunology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2012.00112

DOI=10.3389/fimmu.2012.00112

ISSN=1664-3224

ABSTRACT=<p>Mast cells play a key role in allergic reaction and disorders through the high affinity receptor for IgE (Fc<sub>ε</sub>RI) which is primarily activated by IgE and antigen complex. In humans, mast cells express two types of Fc<sub>ε</sub>RI on the cell surface, tetrameric αβγ<sub>2</sub> and trimeric αγ<sub>2</sub>, whereas in mice, the tetrameric αβγ<sub>2</sub> type is exclusively expressed. In human allergic inflammation lesions, mast cells increase in number and preferentially express the αβγ<sub>2</sub> type Fc<sub>ε</sub>RI. By contrast, in the lesion of non-allergic inflammation, mast cells mainly express the αγ<sub>2</sub>type. Since the β chain amplifies the expression and signaling of FcεRI, mast cell effector functions and allergic reaction <italic>in vivo</italic> are enhanced in the presence of the β chain. In contrast, a truncated β chain-isoform (βT) inhibits FcεRI surface expression. The human Fc<sub>ε</sub>RIβ gene contains seven exons and a repressor element located in the forth intron, through which Fc<sub>ε</sub>RIβ transcription is repressed in the presence of GM-CSF. Regarding the additional signal regulatory function of the β chain, the β chain ITAM has dual (positive and negative) functions in the regulation of the mast cell activation. Namely, the Fc<sub>ε</sub>RIβ chain ITAM enhances the mast cell activation signal triggered by a low-intensity (weak) stimulation whereas it suppresses the signal triggered by high-intensity (strong) stimulation. In an oxazolone-induced mouse CHS model, IgE-mediated mast cell activation is required and the β chain ITAM is crucially involved. Adenosine receptor, one of the GPCRs, triggers a synergistic degranulation response with FcεRI in mast cells, for which the β chain ITAM critically plays positive role, possibly reflecting the <italic>in vivo</italic> allergic response. These regulatory functions of the FcεRIβ ITAM finely tune FcεRI-induced mast cell activation depending on the stimulation strength, enabling the Fc<sub>ε</sub>RIβ chain to become a potential molecular target for the development of new strategies for therapeutic interventions for allergies.</p>