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

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

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 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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Calcium Signaling / genetics
  • Calcium Signaling / immunology
  • Hypersensitivity / immunology*
  • Hypersensitivity / therapy
  • Immunity, Active / genetics
  • Immunity, Innate / genetics
  • Immunoglobulin E / genetics
  • Immunoglobulin E / metabolism
  • Immunosuppression
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Knockout
  • Passive Cutaneous Anaphylaxis / genetics
  • Passive Cutaneous Anaphylaxis / immunology*
  • Receptors, IgE / immunology*
  • Receptors, IgE / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Mona protein, mouse
  • Receptors, IgE
  • Toll-Like Receptors
  • Immunoglobulin E