Inhibition of Notch signalling has ability to alter the proximal and distal TCR signalling events in human CD3+ αß T-cells.
Mol Immunol
; 92: 116-124, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-29078088
ABSTRACT
The Notch signalling pathway is an important regulator of T cell function and is known to regulate the effector functions of T cells driven by T cell receptor (TCR). However, the mechanism integrating these pathways in human CD3+ αß T cells is not well understood. The present study was carried out to investigate how Notch and TCR driven signalling are synchronized in human αß T cells. Differential expression of Notch receptors, ligands, and target genes is observed on human αß T cells which are upregulated on stimulation with α-CD3/CD28 mAb. Inhibition of Notch signalling by GSI-X inhibited the activation of T cells and affected proximal T cell signalling by regulating CD3-ζ chain expression. Inhibition of Notch signalling decreased the protein expression of CD3-ζ chain and induced expression of E3 ubiquitin ligase (GRAIL) in human αß T cells. Apart from affecting proximal TCR signalling, Notch signalling also regulated the distal TCR signalling events. In the absence of Notch signalling, α-CD3/CD28 mAb induced activation and IFN-γ production by αß T cells was down-modulated. The absence of Notch signalling in human αß T cells inhibited proliferative responses despite strong signalling through TCR and IL-2 receptor. This study shows how Notch signalling cooperates with TCR signalling by regulating CD3-ζ chain expression to support proliferation and activation of human αß T cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Transdução de Sinais
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Receptores de Antígenos de Linfócitos T alfa-beta
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Complexo CD3
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Proliferação de Células
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Receptores Notch
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia