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Am J Respir Cell Mol Biol ; 44(4): 448-55, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20508071

ABSTRACT

CD4(+) T cells, particularly T helper (Th) 2 cells, play a pivotal role in the pathophysiology of allergic asthma. Suppressor of cytokine signaling (SOCS) proteins control the balance of CD4(+) T cell differentiation. Mice that lack SOCS3 in T cells by crossing SOCS3-floxed mice with Lck-Cre-transgenic mice have reduced allergen-induced eosinophilia in the airways. Here, we studied the effects of SOCS3 silencing with small interfering (si) RNA in primary CD4(+) T cells on Th2 cell differentiation and on asthmatic responses in mice. Th2 cells were generated from ovalbumin (OVA)-specific T cell receptor-transgenic mice in vitro and transferred into recipient mice. Transfection of SOCS3-specific siRNA attenuated Th2 response in vitro. Adoptive transfer of SOCS3-siRNA T cells exhibited markedly suppressed airway hyperresponsiveness and eosinophilia after OVA challenge, with a concomitant decrease in OVA-specific CD4(+) T cell accumulation in the airways. To investigate the mechanism of this impaired CD4(+) T cell accumulation, we inactivated SOCS3 of T cells by crossing SOCS3-floxed (SOCS3(flox/flox)) mice with CD4-Cre transgenic mice. CD4-Cre × SOCS3(flox/flox) mice exhibited fewer IL-4-producing cells and more reduced eosinophil infiltration in bronchoalveolar lavage fluids than control mice in a model of OVA-induced asthma. Expression of CCR3 and CCR4 in CD4(+) T cells was decreased in CD4-Cre × SOCS3(flox/flox) mice. CCR4 expression was also decreased in CD4(+) T cells after transfer of SOCS3 siRNA-treated T cells. These findings suggest that the therapeutic modulation of SOCS3 expression in CD4(+) T cells might be effective in preventing the development of allergic asthma.


Subject(s)
Asthma/immunology , Asthma/physiopathology , Bronchial Hyperreactivity/immunology , CD4-Positive T-Lymphocytes/metabolism , RNA, Small Interfering/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Adoptive Transfer , Animals , CD4-Positive T-Lymphocytes/immunology , Cell Differentiation , Disease Models, Animal , Down-Regulation , Heterozygote , Lymphocyte Depletion , Mice , Receptors, CCR3/metabolism , Receptors, CCR4/metabolism , Suppressor of Cytokine Signaling 3 Protein , Th2 Cells/cytology , Th2 Cells/immunology
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