The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.

Autor: Dunbar H; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland., Hawthorne IJ; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland., Tunstead C; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland., Dunlop M; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland., Volkova E; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland., Weiss DJ; Department of Medicine, 226 Health Sciences Research Facility, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA., Santos CCD; The Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada.; Institute of Medical Sciences and Interdepartmental Division of Critical Care, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Armstrong ME; Department of Medicine, Trinity College Dublin and Tallaght Hospital, Dublin, Ireland., Donnelly SC; Department of Medicine, Trinity College Dublin and Tallaght Hospital, Dublin, Ireland., English K; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.; Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Nov 06, pp. e202451205. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1002/eji.202451205
Abstrakt: Enhancing mesenchymal stromal cell (MSC) therapeutic efficacy through licensing with proinflammatory cytokines is now well established. We have previously shown that macrophage migration inhibitory factor (MIF)-licensed MSCs exerted significantly enhanced therapeutic efficacy in reducing inflammation in house dust mite (HDM)-driven allergic asthma. Soluble mediators released into the MSC secretome boast cytoprotective properties equal to those associated with the cell itself. In asthma, epithelial barrier damage caused by the inhalation of allergens like HDM drives goblet cell hyperplasia. Vascular endothelial growth factor (VEGF) plays a pivotal role in the repair and maintenance of airway epithelial integrity. Human bone marrow-derived MSCs expressed the MIF receptors CD74, CXCR2, and CXCR4. Endogenous MIF from high MIF expressing CATT 7 bone marrow-derived macrophages increased MSC production of VEGF through the MIF CXCR4 chemokine receptor, where preincubation with CXCR4 inhibitor mitigated this effect. CATT 7 -MIF licensed MSC conditioned media containing increased levels of VEGF significantly enhanced bronchial epithelial wound healing via migration and proliferation in vitro. Blocking VEGFR2 or the use of mitomycin C abrogated this effect. Furthermore, CATT 7 -MIF MSC CM significantly decreased goblet cell hyperplasia after the HDM challenge in vivo. This was confirmed to be VEGF-dependent, as the use of anti-human VEGF neutralising antibody abrogated this effect. Overall, this study highlights that MIF-licenced MSCs show enhanced production of VEGF, which has the capacity to repair the lung epithelium.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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