Mesenchymal stromal cells dampen trained immunity in house dust mite-primed macrophages expressing human macrophage migration inhibitory factor polymorphism.

Autor: Dunbar H; Department of Biology, Maynooth University, Maynooth, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland., Hawthorne IJ; Department of Biology, Maynooth University, Maynooth, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland., Tunstead C; Department of Biology, Maynooth University, Maynooth, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland., McNamee EN; Department of Biology, Maynooth University, Maynooth, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland., Weiss DJ; Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA., Armstrong ME; Department of Medicine, Trinity College Dublin and Tallaght University Hospital, Dublin, Ireland., Donnelly SC; Department of Medicine, Trinity College Dublin and Tallaght University Hospital, Dublin, Ireland., English K; Department of Biology, Maynooth University, Maynooth, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland. Electronic address: karen.english@mu.ie.
Jazyk: angličtina
Zdroj: Cytotherapy [Cytotherapy] 2024 Oct; Vol. 26 (10), pp. 1245-1251. Date of Electronic Publication: 2024 May 19.
DOI: 10.1016/j.jcyt.2024.05.010
Abstrakt: 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) CATT 7 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 CATT 7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT 7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-α) 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 CATT 7 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-α 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 CATT 7 mice in a model of allergic airway inflammation.
Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article.
(Copyright © 2024 International Society for Cell & Gene Therapy. All rights reserved.)
Databáze: MEDLINE
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