1. Selective impairment of Fc{varepsilon}RI-mediated allergic reaction in Gads-deficient mice.
- Author
-
Sho Yamasaki, Mitsuyo Takase-Utsugi, Eri Ishikawa, Machie Sakuma, Keigo Nishida, Takashi Saito, and Osami Kanagawa
- Subjects
HEMATOPOIETIC agents ,MAST cells ,PROTEIN analysis ,IMMUNE response ,LABORATORY mice ,IMMUNOGLOBULIN E ,BACTERIAL diseases - Abstract
Gads is a Grb2-like adaptor protein expressed in hematopoietic cells. We demonstrated that mast cells from Gads−/− mice have selective functional defects. Bone marrow-derived mast cells from Gads−/− mice failed to induce Ca2+ mobilization, degranulation and cytokine production upon cross-linking of FcεRI. In vivo passive cutaneous anaphylaxis was also greatly impaired in Gads−/− mice. In contrast, Gads was dispensable for Toll-like receptor-mediated cytokine production in mast cells. Accordingly, mast cell-dependent resistance to acute peritoneal bacterial infection is not reduced in Gads−/− mice in vivo. Moreover, mature T and B cell responses and antibody production upon immunization were apparently normal in Gads−/− mice. Thus, inhibition of Gads in vivo would suppress the IgE-mediated allergic reaction with minimum adverse effects on both innate and acquired immune responses, and Gads could be an ideal target for the control of allergic responses. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF