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Inflammation Research
Published in: Inflammation Research 9/2019

Open Access 01-09-2019 | Spondyloarthropathy | Original Research Paper

ER stress abrogates the immunosuppressive effect of IL-10 on human macrophages through inhibition of STAT3 activation

Authors: Ivo S. Hansen, Josca M. Schoonejans, Lathees Sritharan, Johan A. van Burgsteden, Carmen A. Ambarus, Dominique L. P. Baeten, Jeroen den Dunnen

Published in: Inflammation Research | Issue 9/2019

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Abstract

Objective and design

To determine whether ER stress affects the inhibitory pathways of the human immune system, particularly the immunosuppressive effect of IL-10 on macrophages.

Material or subjects

In vitro stimulation of human monocyte-derived macrophages.

Treatment

Cells were stimulated with TLR ligands and IL-10, while ER stress was induced using thapsigargin or tunicamycin.

Methods

mRNA expression was determined using qPCR, while cytokine protein production was measured using ELISA. Protein expression of receptors and transcription factors was determined using flow cytometry. Student’s t test was used for statistics.

Results

While under normal conditions IL-10 potently suppresses pro-inflammatory cytokine production by LPS-stimulated macrophages, we demonstrate that ER stress counteracts the immunosuppressive effects of IL-10, leading to increased pro-inflammatory cytokine production. We identified that ER stress directly interferes with IL-10R signaling by reducing STAT3 phosphorylation on Tyr705, which thereby inhibits the expression of SOCS3. Moreover, we show that ER stress also inhibits STAT3 activation induced by other receptors such as IL-6R.

Conclusions

Combined, these data uncover a new general mechanism by which ER stress promotes inflammation. Considering its potential involvement in the pathogenesis of diseases such as Crohn’s disease and spondyloarthritis, targeting of this mechanism may provide new opportunities to counteract inflammation.
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Metadata
Title
ER stress abrogates the immunosuppressive effect of IL-10 on human macrophages through inhibition of STAT3 activation
Authors
Ivo S. Hansen
Josca M. Schoonejans
Lathees Sritharan
Johan A. van Burgsteden
Carmen A. Ambarus
Dominique L. P. Baeten
Jeroen den Dunnen
Publication date
01-09-2019
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 9/2019
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-019-01261-9

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