Selective impairment of FcepsilonRI-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 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.
Yamasaki
Sho
S
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Takase-Utsugi
Mitsuyo
M
Ishikawa
Eri
E
Sakuma
Machie
M
Nishida
Keigo
K
Saito
Takashi
T
Kanagawa
Osami
O
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology* / Q000628:therapy; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism; D007165:Immunosuppression Therapy; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C498726:Mona protein, mouse; D017455:Receptors, IgE; D051193:Toll-Like Receptors; D007073:Immunoglobulin E