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Int Immunol. 2008 Oct;20(10):1289-97. doi: 10.1093/intimm/dxn085. Epub 2008 Jul 29.

Selective impairment of FcepsilonRI-mediated allergic reaction in Gads-deficient mice.

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Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.


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 Ca(2+) mobilization, degranulation and cytokine production upon cross-linking of FcepsilonRI. 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.

[Indexed for MEDLINE]

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