Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB.
Immunol Lett
; 212: 14-21, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31216428
ABSTRACT
IL-10 is a suppressive cytokine that has been implicated in the pathophysiology of autoimmune disorders and can be produced by different cell types such as regulatory B-cells. Our previous work showed that under inflammatory condition MZ B-cells differentiated into IL-10 producing cells and contributed to the downregulation of collagen-induced arthritis, while follicular B-cells failed to do so. Based on these observations, we aimed to investigate how inflammatory signals mediated through the BCR, TLR9 and IFN-γ receptors trigger IL-10 production in MZ B-cells but leave FO B-cells unresponsive. We particularly focused on the CREB transcription factor as it is involved in all three signalling cascades and analysed its contribution to IL-10 production. Our results demonstrate that the IL-10 production of MZ B-cells induced by the BCR, TLR9 and IFN-γ receptors is mediated by CREB. We showed that the activation of CREB is prolonged in MZ B-cells while the transcription factor only transiently phosphorylated in FO B-cells. The sustained phosphorylation of CREB is clearly associated with its prolonged binding to molecular partner CBP, whereas inhibition of their association decreased IL-10 production. We assume that sustained activation of CREB is required for IL-10 production by B-cells under inflammatory conditions.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Regulação da Expressão Gênica
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Subpopulações de Linfócitos B
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Interleucina-10
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
Limite:
Animals
Idioma:
En
Revista:
Immunol Lett
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Hungria