Journal article
GM-CSF primes proinflammatory monocyte responses in Ankylosing Spondylitis
- Abstract:
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Objectives: GM-CSF is a pro-inflammatory cytokine with multiple actions predominantly on myeloid cells. Enhanced GM-CSF expression by lymphocytes from patients with Ankylosing Spondylitis (AS) has recently been described, however, its potential pathogenic role(s) in AS are unknown.
Methods: The effects of GM-CSF on TNF, IL-23 and CCL17 production by blood, PBMCs and isolated CD14+ monocytes from AS patients and healthy controls (HCs) were studied using ELISA. Serum CCL17 and GM-CSF and T cell GM-CSF production were studied in AS patients including pre-and on TNFi therapy.
Results: GM-CSF markedly increased TNF production by LPS-stimulated whole blood, peripheral blood mononuclear cells (PBMC) and purified monocytes from AS patients, with two hours GM-CSF exposure sufficient for monocyte “priming”. Blocking of GM-CSF significantly reduced the production of TNF by whole blood from AS patients but not HCs. GM-CSF priming increased IL-23 production from LPS-stimulated AS and HC whole blood five-fold, with baseline and stimulated IL-23 levels being significantly higher in AS whole blood. GM-CSF also stimulated CCL17 production from AS and HC blood and CCL17 levels were elevated in AS plasma. GM-CSF could be detected in plasma from 14/46 (30%) AS patients compared to 3/18 (17%) HC.
Conclusion: We provide evidence that GM-CSF primes TNF and IL-23 responses in myeloid cells from AS patients and HC. We also show CCL17 levels, downstream of GM-CSF, were elevated in plasma samples of AS patients. Taken together these observations are supportive of GM-CSF neutralisation as a potential novel therapeutic approach for the treatment of AS.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1020.9KB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2020.01520
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 11
- Article number:
- 1520
- Publication date:
- 2020-07-16
- Acceptance date:
- 2020-06-09
- DOI:
- ISSN:
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1664-3224
- Language:
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English
- Keywords:
- Pubs id:
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1110978
- Local pid:
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pubs:1110978
- Deposit date:
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2020-06-09
- ARK identifier:
Terms of use
- Copyright holder:
- Shi et al.
- Copyright date:
- 2020
- Rights statement:
- © 2020 Shi, Chen, Ridley, Zaarour, Brough, Caucci, Smith and Bowness. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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