Mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2-dependent pathways are essential for CD8+ T cell-mediated airway hyperresponsiveness and inflammation.
J Allergy Clin Immunol
; 123(1): 249-57, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-19130938
ABSTRACT
BACKGROUND:
Ligation of the leukotriene B(4) (LTB(4)) receptor 1 on effector memory CD8(+) T cells by LTB(4) is important for the recruitment of CD8(+) T cells into the airways, which appears central to the induction of airway hyperresponsiveness (AHR) and allergic inflammation. Phosphorylation of extracellular signal-regulated kinase (ERK) is important in activation and cytokine production from many cell types.OBJECTIVE:
The roles of ERKs in effector CD8(+) T-cell function and on CD8(+) T cell-mediated AHR were determined.METHODS:
Effector CD8(+) T cells were generated from OVA(257-264) (SIINFEKL) peptide-primed mononuclear cells from OT-1 mice. The effects of U0126, an ERK inhibitor, on effector CD8(+) T-cell function and on CD8(+) T cell-mediated AHR and allergic inflammation were examined.RESULTS:
Pretreatment of effector CD8(+) T cells with U0126 suppressed anti-CD3/anti-CD28-induced ERK1/2 phosphorylation and cytokine production, but did not affect LTB(4)-induced Ca(2+) mobilization or chemotaxis. Adoptive transfer of U0126-treated CD8(+) T cells into sensitized mice before secondary allergen challenge resulted in significant decreases in AHR, eosinophilic inflammation, goblet cell metaplasia, and IL-5 and IL-13 levels in bronchoalveolar lavage fluid of recipient mice. The number of transferred CD8(+) T cells accumulating in bronchoalveolar lavage fluid or lungs was unaffected by treatment.CONCLUSION:
ERK1/2-dependent pathways are essential for the effector functions of CD8(+) T cells, including T(H)2 cytokine production, allergic inflammation, and development of AHR. Inhibition of ERK1/2 signaling has potential therapeutic benefit in preventing CD8(+) T cell-mediated AHR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipersensibilidade Respiratória
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Quimiotaxia
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Linfócitos T CD8-Positivos
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Proteína Quinase 1 Ativada por Mitógeno
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Sistema de Sinalização das MAP Quinases
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Proteína Quinase 3 Ativada por Mitógeno
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos