Abstract
The cross-linking of FcεRI on mast cells by IgE and antigen (Ag) initiates activation cascades that lead to allergic responses. FcεRI is composed of an α and a β monomer, and a γ homodimer, and the β and γ chains possess immunoreceptor tyrosine-based activation motifs (ITAMs). Through the phosphorylation of ITAMs, activation signals are transmitted intracellularly. Mast cells are also activated through FcγR-FcRγ by an immune complex, which often results in hypersensitivity. We defined FcRγ-signal-dependent and -independent mast cell responses by analyzing FcRγ-/- mice reconstituted with mutant FcRγ-ITAM. Most of the FcεRI-mediated activations by IgE(+Ag), such as induction of degranulation, arachidonic acid metabolism, cytokine production and systemic anaphylaxis, are dependent on signaling through FcRγ-ITAM. On the other hand, IgE without Ag induces the upregulation of surface FcεRI expression and mast cell survival. The former is independent of and the latter is dependent on FcRγ-ITAM. As a molecular mechanism for the generation of diverse responses through FcεRI, we found that the quantity and the duration of the FcRγ signal determine the degranulation and the survival of mast cells, respectively. Furthermore, such a sustained FcRγ-signal-induced survival is mediated by autocrine cytokine production. In this review, the in vivo function of FcRγ and the signal regulation for the distinct responses of mast cells through FcεRI are discussed.
| Original language | English |
|---|---|
| Pages (from-to) | 22-31 |
| Number of pages | 10 |
| Journal | Chemical Immunology and Allergy |
| Volume | 87 |
| DOIs | |
| Publication status | Published - Dec 1 2005 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Medicine(all)
Cite this
Regulation of mast cell activation through FcεRI. / Yamasaki, Sho; Saito, Takashi.
In: Chemical Immunology and Allergy, Vol. 87, 01.12.2005, p. 22-31.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Regulation of mast cell activation through FcεRI
AU - Yamasaki, Sho
AU - Saito, Takashi
PY - 2005/12/1
Y1 - 2005/12/1
N2 - The cross-linking of FcεRI on mast cells by IgE and antigen (Ag) initiates activation cascades that lead to allergic responses. FcεRI is composed of an α and a β monomer, and a γ homodimer, and the β and γ chains possess immunoreceptor tyrosine-based activation motifs (ITAMs). Through the phosphorylation of ITAMs, activation signals are transmitted intracellularly. Mast cells are also activated through FcγR-FcRγ by an immune complex, which often results in hypersensitivity. We defined FcRγ-signal-dependent and -independent mast cell responses by analyzing FcRγ-/- mice reconstituted with mutant FcRγ-ITAM. Most of the FcεRI-mediated activations by IgE(+Ag), such as induction of degranulation, arachidonic acid metabolism, cytokine production and systemic anaphylaxis, are dependent on signaling through FcRγ-ITAM. On the other hand, IgE without Ag induces the upregulation of surface FcεRI expression and mast cell survival. The former is independent of and the latter is dependent on FcRγ-ITAM. As a molecular mechanism for the generation of diverse responses through FcεRI, we found that the quantity and the duration of the FcRγ signal determine the degranulation and the survival of mast cells, respectively. Furthermore, such a sustained FcRγ-signal-induced survival is mediated by autocrine cytokine production. In this review, the in vivo function of FcRγ and the signal regulation for the distinct responses of mast cells through FcεRI are discussed.
AB - The cross-linking of FcεRI on mast cells by IgE and antigen (Ag) initiates activation cascades that lead to allergic responses. FcεRI is composed of an α and a β monomer, and a γ homodimer, and the β and γ chains possess immunoreceptor tyrosine-based activation motifs (ITAMs). Through the phosphorylation of ITAMs, activation signals are transmitted intracellularly. Mast cells are also activated through FcγR-FcRγ by an immune complex, which often results in hypersensitivity. We defined FcRγ-signal-dependent and -independent mast cell responses by analyzing FcRγ-/- mice reconstituted with mutant FcRγ-ITAM. Most of the FcεRI-mediated activations by IgE(+Ag), such as induction of degranulation, arachidonic acid metabolism, cytokine production and systemic anaphylaxis, are dependent on signaling through FcRγ-ITAM. On the other hand, IgE without Ag induces the upregulation of surface FcεRI expression and mast cell survival. The former is independent of and the latter is dependent on FcRγ-ITAM. As a molecular mechanism for the generation of diverse responses through FcεRI, we found that the quantity and the duration of the FcRγ signal determine the degranulation and the survival of mast cells, respectively. Furthermore, such a sustained FcRγ-signal-induced survival is mediated by autocrine cytokine production. In this review, the in vivo function of FcRγ and the signal regulation for the distinct responses of mast cells through FcεRI are discussed.
UR - http://www.scopus.com/inward/record.url?scp=25144484012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25144484012&partnerID=8YFLogxK
U2 - 10.1159/000087568
DO - 10.1159/000087568
M3 - Review article
C2 - 16107760
AN - SCOPUS:25144484012
VL - 87
SP - 22
EP - 31
JO - Progress in Allergy
JF - Progress in Allergy
SN - 1660-2242
ER -