B lymphocyte-induced maturation protein 1 controls TH9 cell development, IL-9 production, and allergic inflammation.
J Allergy Clin Immunol
; 143(3): 1119-1130.e3, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30096391
ABSTRACT
BACKGROUND:
The transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) has a key role in terminal differentiation in various T-cell subtypes. However, whether Blimp-1 regulates TH9 differentiation and its role in allergic inflammation are unknown.OBJECTIVE:
We aimed to investigate the role of Blimp-1 in TH9 differentiation and in the pathogenesis of allergic airway inflammation.METHODS:
In vitro TH9 differentiation, flow cytometry, ELISA, and real-time PCR were used to investigate the effects of Blimp-1 on TH9 polarization. T cell-specific Blimp-1-deficient mice, a model of allergic airway inflammation, and T-cell adoptive transfer to recombination-activating gene 1 (Rag-1)-/- mice were used to address the role of Blimp-1 in the pathogenesis of allergic inflammation.RESULTS:
We found that Blimp-1 regulates TH9 differentiation because deleting Blimp-1 increased IL-9 production in CD4+ T cells in vitro. In addition, we showed that in T cell-specific Blimp-1-deficient mice, deletion of Blimp-1 in T cells worsened airway disease, and this worsening was inhibited by IL-9 neutralization. In asthmatic patients CD4+ T cells in response to TGF-ß plus IL-4 increased IL-9 expression and downregulated Blimp-1 expression compared with expression in healthy control subjects. Blimp-1 overexpression in human TH9 cells inhibited IL-9 expression.CONCLUSION:
Blimp-1 is a pivotal negative regulator of TH9 differentiation and controls allergic inflammation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Diferenciação Celular
/
Interleucina-9
/
Linfócitos T Auxiliares-Indutores
/
Fator 1 de Ligação ao Domínio I Regulador Positivo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil