TY - JOUR
T1 - Selective impairment of FcεRI-mediated allergic reaction in Gads-deficient mice
AU - Yamasaki, Sho
AU - Takase-Utsugi, Mitsuyo
AU - Ishikawa, Eri
AU - Sakuma, Machie
AU - Nishida, Keigo
AU - Saito, Takashi
AU - Kanagawa, Osami
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
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U2 - 10.1093/intimm/dxn085
DO - 10.1093/intimm/dxn085
M3 - Article
C2 - 18664516
AN - SCOPUS:52949096542
VL - 20
SP - 1289
EP - 1297
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 10
ER -