Rgs13 inhibits IgE-mediated allergic responses (37.5)

• Published in: The Journal of immunology (1950) 2007-04, Vol.178 (1_Supplement), p.S19-S19
• Main Authors: Bansal, Geetanjali, Xie, Zhihui, Druey, Kirk
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.Supp.37.5

Mast cells (MCs) evoke immediate hypersensitivity by degranulating in response to antigen (Ag) exposure and releasing preformed mediators such as histamine and leukotreines. Classically, the high affinity immune receptor for immunoglobulin E (FcεRI) mediates MC degranulation and anaphylaxis in response to antigen. In addition, various G protein coupled receptors (GPCRs) on MCs such as those for adenosine and sphingosine-1-phosphate (S1P) may also activate MCs. Since GPCR signaling is inhibited by Regulator of G protein Signaling (RGS) proteins, we studied the potential regulation of MC activation by RGS proteins. We identified Rgs1, 8, 13 and 18 in murine bone marrow-derived MCs (BMMCs). Rgs13−/− (KO) mice with LacZ knock-in were generated. Surprisingly, G protein-mediated degranulation induced by either adenosine or S1P was similar in WT and KO mice. In contrast, IgE/Ag -dependent degranulation and intracellular Ca++ flux as well as in vivo passive cutaneous anaphylaxis responses were significantly higher in KO BMMCs suggesting that Rgs13 affects IgE/Ag dependent pathway rather that GPCR-mediated pathway leading to MC activation. Reconstitution of KO BMMCs with WT Rgs13 inhibited degranulation to IgE/Ag. Analysis of effectors downstream of FcεRI revealed that Rgs13 interacts with PI3K and inhibits its activation in response to IgE/Ag. Thus, Rgs13 could represent a new therapeutic target for MC-dependent allergic responses. Work was funded by DIR, NIAID/NIH.