Projects per year
Abstract
Increasing evidence has linked dysregulated IL-10 production by IL-10+ve B cells to autoimmunity, highlighting the importance of improving the understanding of the regulation of IL-10 production in these cells. In both B cells and myeloid cells, IL-10 can be produced in response to Toll-like receptor (TLR) agonists. In macrophages, previous studies have established that mitogen- and stress-activated protein kinases (MSKs) regulate IL-10 production via the phosphorylation of cAMP response element-binding (CREB) protein on the IL-10 promoter. We found here that although MSKs are activated in peritoneal B cells in response to TLR4 agonists, neither MSKs nor CREB are required for IL-10 production in these cells. Using a combination of chemical inhibitors and knockout mice, we found that IL-10 induction in B cells was regulated by an ERK1/2- and p90 ribosomal S6 kinases (RSKs)-dependent mechanism, unlike in macrophages in which RSK was not required. This observation highlights fundamental differences in the signaling controlling IL-10 production in B cells and macrophages, even though these two cell types respond to a common TLR stimulus.
Original language | English |
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Pages (from-to) | 2302-2317 |
Number of pages | 16 |
Journal | Journal of Biological Chemistry |
Volume | 293 |
Issue number | 7 |
Early online date | 11 Dec 2017 |
DOIs | |
Publication status | Published - 16 Feb 2018 |
Keywords
- Journal article
- cAMP response element-binding protein (CREB)
- Extracellular-signal-regulated kinase (ERK)
- p38 MAPK
- RSK
- Toll-like receptor 4 (TLR4)
- Interleukin 10
- MSK1
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Cell Biology
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Dive into the research topics of 'Differential control of Toll-like receptor 4-induced interleukin-10 induction in macrophages and B cells reveals a role for p90 ribosomal S6 kinases'. Together they form a unique fingerprint.Projects
- 3 Finished
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The Role of the MSK-CREB Axis in IL-23 Production and Initiation of Arthritis
Arthur, S. (Investigator)
1/04/14 → 31/03/17
Project: Research
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Understanding the Molecular Pathways that Underlie Dectin-1 Mediated Cytokine Responses
Arthur, S. (Investigator)
1/01/14 → 30/11/18
Project: Research