BACKGROUND: Type 2 T helper lymphocytes (Th2 cells) and their cytokine products are important in the pathogenesis of @entity565 . OBJECTIVE: To examine the contribution of the @entity9094 pathway, involved in Th2 cytokine signalling, to the development of lesions of chronic @entity565 . METHODS: BALB/c @entity19 sensitized to ovalbumin were chronically challenged by inhalational of low mass concentrations of antigen for 6 weeks. @entity75 in wild-type @entity19 were compared with those in @entity9094 -deficient @entity19 and in @entity58 /13 double-deficient @entity19 by histomorphometry and immunohistochemistry. Airway responses to @entity2710 were evaluated by whole-body plethysmography. Cytokine production by peribronchial lymph node cells was quantified by enzyme immunoassay. RESULTS: @entity9094 -/- @entity19 developed a variety of airway lesions that were at least equivalent to those in wild-type @entity19 , including accumulation of intraepithelial eosinophils and of chronic inflammatory cells in the lamina propria, subepithelial @entity82 and epithelial thickening. In addition, @entity9094 -/- @entity19 exhibited exaggerated airway hyper-reactivity (AHR) compared to wild-type animals. This was despite a shift from a Th2 to a Th1 pattern of immunoglobulin production by plasma cells in the inflammatory infiltrate and diminished mucous cell @entity1373 / @entity4648 , together with increased production of @entity60 by peribronchial lymph node cells, consistent with absence of signalling via the @entity9094 pathway. In contrast, gene-targeted @entity58 /13-/- @entity19 exhibited markedly diminished eosinophil recruitment and airway remodelling, as well as absence of AHR. CONCLUSIONS: In this model, the effects of @entity9094 deficiency were in marked contrast to the @entity32 and AHR described in models of @entity32 . These results, which provide evidence of @entity9094 -independent AHR in an inhalational challenge model of chronic @entity565 , emphasize the critical effector roles of @entity58 and @entity1312 , as well as the need to use appropriate models to understand cytokine signalling pathways that may be potential therapeutic targets in @entity565 .

Dissociation of T helper type 2 cytokine-dependent airway lesions from XXXX signalling in experimental chronic @entity565 .

@entity32 :: ('MESH:D007249', 'Disease') :: ['allergic bronchopulmonary inflammation', 'suppression of inflammation'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity75 :: ('MESH:D001927', 'Disease') :: ['Airway lesions'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['hyperplasia'] @entity60 :: ('15978(Tax:10090)', 'Gene') :: ['IFN-gamma'] @entity9094 :: ('20852(Tax:10090)', 'Gene') :: ['signal transducer and activator of transcription (STAT) 6', 'STAT6'] @entity4648 :: ('MESH:D008679', 'Disease') :: ['metaplasia'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['IL-4'] @entity1312 :: ('16163(Tax:10090)', 'Gene') :: ['IL-13'] @entity2710 :: ('MESH:D016210', 'Chemical') :: ['methacholine']
@entity9094 :: (20852(Tax:10090),Gene) :: ['signal transducer and activator of transcription 6']
