Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB

Balázs L. Barátki, Krisztina Huber, G. Sármay, J. Matkó, Dorottya Kövesdi

Research output: Article

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalImmunology letters
Volume212
DOIs
Publication statusPublished - aug. 1 2019

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Interleukin-10
B-Lymphocytes
Toll-Like Receptor 9
Regulatory B-Lymphocytes
Transcription Factors
Experimental Arthritis
Down-Regulation
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB. / Barátki, Balázs L.; Huber, Krisztina; Sármay, G.; Matkó, J.; Kövesdi, Dorottya.

In: Immunology letters, Vol. 212, 01.08.2019, p. 14-21.

Research output: Article

Barátki, Balázs L. ; Huber, Krisztina ; Sármay, G. ; Matkó, J. ; Kövesdi, Dorottya. / Inflammatory signal induced IL-10 production of marginal zone B-cells depends on CREB. In: Immunology letters. 2019 ; Vol. 212. pp. 14-21.
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