Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma.
J Exp Med
; 195(11): 1433-44, 2002 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-12045241
ABSTRACT
Interleukin (IL)-5 and IL-13 are thought to play key roles in the pathogenesis of asthma. Although both cytokines use eotaxin to regulate eosinophilia, IL-13 is thought to operate a separate pathway to IL-5 to induce airways hyperreactivity (AHR) in the allergic lung. However, identification of the key pathway(s) used by IL-5 and IL-13 in the disease process is confounded by the failure of anti-IL-5 or anti-IL-13 treatments to completely inhibit the accumulation of eosinophils in lung tissue. By using mice deficient in both IL-5 and eotaxin (IL-5/eotaxin(-/-)) we have abolished tissue eosinophilia and the induction of AHR in the allergic lung. Notably, in mice deficient in IL-5/eotaxin the ability of CD4(+) T helper cell (Th)2 lymphocytes to produce IL-13, a critical regulator of airways smooth muscle constriction and obstruction, was significantly impaired. Moreover, the transfer of eosinophils to IL-5/eotaxin(-/-) mice overcame the intrinsic defect in T cell IL-13 production. Thus, factors produced by eosinophils may either directly or indirectly modulate the production of IL-13 during Th2 cell development. Our data show that IL-5 and eotaxin intrinsically modulate IL-13 production from Th2 cells and that these signaling systems are not necessarily independent effector pathways and may also be integrated to regulate aspects of allergic disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Linfócitos T CD4-Positivos
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Interleucina-5
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Hiper-Reatividade Brônquica
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Interleucina-13
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Quimiocinas CC
/
Eosinofilia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Austrália