Impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation.
Am J Physiol Lung Cell Mol Physiol
; 313(3): L592-L601, 2017 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-28619762
ABSTRACT
CD4+ T-cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+ T-lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here, we investigated the role of TNFR2 in allergic airway inflammation. The mouse model was generated by immunization with ovalbumin and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+ T-cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid. Impaired TNFR2 signaling promoted Th2 and Th17 polarization but inhibited Th1 and CD4+CD25+ T-cell differentiation in vivo. Furthermore, TNFR2 signaling inhibition promoted Th2 and Th17 polarization in vitro, which may occur through the activation of TNF receptor-associated factor 2 and NF-κB signaling. Therefore, our findings indicate that impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neumonía
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Transducción de Señal
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Factor de Necrosis Tumoral alfa
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Células Th2
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Receptores Tipo II del Factor de Necrosis Tumoral
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Células Th17
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Hipersensibilidad
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article