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 vitroandtransferred into recipient mice. Transfection of SOCS3-specific siRNA attenuated Th2 response in vitro. Adoptive transfer of SOCS3-siRNAT 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 x 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 x SOCS3flox/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.
|ジャーナル||American journal of respiratory cell and molecular biology|
|出版ステータス||Published - 2011 4 1|
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology