Dunbar, Hazel and Hawthorne, Ian J. and Tunstead, Courteney and McNamee, Eóin N. and Weiss, Daniel J. and Armstrong, Michelle E. and Donnelly, Seamas C. and English, Karen
(2024)
Mesenchymal stromal cells dampen trained immunity in house dust mite-primed macrophages expressing human macrophage migration inhibitory factor polymorphism.
Cytotherapy, 26 (10).
pp. 1245-1251.
ISSN 1465-3249
Abstract
Background: Trained immunity results in long-term immunological memory, provoking a faster and greater
immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have
previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the
human macrophage migration inhibitory factor (MIF) CATT7 functional polymorphism.
Aim: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained
immunity both in vitro and in vivo.
Methods: Compared with wild-type mice, in vivo HDM-primed bone marrow-derived macrophages (BMDMs)
from CATT7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-a) being significantly decreased in a cyclooxygenase 2 (COX-2)-dependent manner.
Interestingly, interleukin 6 (IL-6) was suppressed by MSCs independently of COX-2. In an in vitro training assay,
MSCs significantly abrogated the enhanced production of pro-inflammatory cytokines by HDM-trained CATT7
BMDMs when co-cultured at the time of HDM stimulus on day 0, displaying their therapeutic efficacy in modulating an overzealous human MIF-dependent immune response. Utilizing an in vivo model of HDM-induced
trained immunity, MSCs administered systemically on day 10 and day 11 suppressed this trained phenomenon
by significantly reducing TNF-a and reducing IL-6 and C-C motif chemokine ligand 17 (CCL17) production.
Conclusions: This novel study elucidates how MSCs can attenuate an MIF-driven, HDM-trained response in
CATT7 mice in a model of allergic airway inflammation
| Item Type: |
Article
|
| Keywords: |
bone marrow-derived macrophages;
house dust mite;
innate training;
macrophage migration inhibitory factor;
mesenchymal stromal cells;
polarization; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
19174 |
| Identification Number: |
https://doi.org/10.1016/j.jcyt.2024.05.010 |
| Depositing User: |
Karen English
|
| Date Deposited: |
11 Nov 2024 17:06 |
| Journal or Publication Title: |
Cytotherapy |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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