RESUMO
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.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Hipersensibilidade/imunologia , Anafilaxia Cutânea Passiva/imunologia , Receptores de IgE/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Sinalização do Cálcio/genética , Sinalização do Cálcio/imunologia , Hipersensibilidade/terapia , Imunidade Ativa/genética , Imunidade Inata/genética , Imunoglobulina E/genética , Imunoglobulina E/metabolismo , Terapia de Imunossupressão , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Camundongos Knockout , Anafilaxia Cutânea Passiva/genética , Receptores de IgE/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/imunologiaRESUMO
A transgenic mouse line expressing Fucci (fluorescent ubiquitination-based cell-cycle indicator) probes allows us to monitor the cell cycle in the hematopoietic system. Two populations with high and low intensities of Fucci signals for Cdt1(30/120) accumulation were identified by FACS analysis, and these correspond to quiescent G0 and cycling G1 cells, respectively. We observed the transition of immune cells between quiescent and proliferative phases in lymphoid organs during differentiation and immune responses.