Selective impairment of FcεRI-mediated allergic reaction in Gads-deficient mice

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. The Japanese Society for Immunology. 2008. All rights reserved.