Ras activation in T cells determines the development of antigen-induced airway hyperresponsiveness and eosinophilic inflammation.
The central role for Th2 cells in the development of Ag-induced airway hyperresponsiveness and eosinophilic inflammation is well documented. We have reported a crucial role for TCR-induced activation of the Ras/extracellular signal-regulated kinase mitogen-activated protein kinase cascade in Th2 cell differentiation. Here, we show that the development of both OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation in a mouse asthma model are attenuated in transgenic mice by the overexpression of enzymatically inactive Ras molecules in T cells. In addition, reduced levels of IL-5 production and eosinophilic inflammation induced by nematode infection (Nippostrongylus brasiliensis or Heligmosomoides polygyrus) were detected. Thus, the level of Ras activation in T cells appears to determine Th2-dependent eosinophilic inflammation and Ag-induced airway hyperresponsiveness.
Shibata
Youichi
Y
Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kamata
Tohru
T
Kimura
Motoko
M
Yamashita
Masakatsu
M
Wang
Chrong-Reen
CR
Murata
Kaoru
K
Miyazaki
Masaru
M
Taniguchi
Masaru
M
Watanabe
Naohiro
N
Nakayama
Toshinori
T
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D011905:Genes, ras; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009351:Nematospiroides dubius; D009559:Nippostrongylus; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017206:Strongylida Infections / Q000150:complications; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015848:Interleukin-5; D010047:Ovalbumin