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Human macrophage mi...
Human macrophage migration inhibitory factor potentiates mesenchymal stromal cell efficacy in a clinically relevant model of allergic asthma
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- Hawthorne, Ian J. (författare)
- Maynooth University
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- Dunbar, Hazel (författare)
- Maynooth University
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- Tunstead, Courteney (författare)
- Maynooth University
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- Schorpp, Tamara (författare)
- Maynooth University
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- Weiss, Daniel J. (författare)
- University of Vermont
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- Enes, Sara Rolandsson (författare)
- Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups
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- dos Santos, Claudia C. (författare)
- University of Toronto
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- Armstrong, Michelle E. (författare)
- Trinity College Dublin
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- Donnelly, Seamas C. (författare)
- Trinity College Dublin
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- English, Karen (författare)
- Maynooth University
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(creator_code:org_t)
- 2023
- 2023
- Engelska 16 s.
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Ingår i: Molecular Therapy. - 1525-0016. ; 31:11, s. 3243-3258
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Current asthma therapies focus on reducing symptoms but fail to restore existing structural damage. Mesenchymal stromal cell (MSC) administration can ameliorate airway inflammation and reverse airway remodeling. However, differences in patient disease microenvironments seem to influence MSC therapeutic effects. A polymorphic CATT tetranucleotide repeat at position 794 of the human macrophage migration inhibitory factor (hMIF) gene has been associated with increased susceptibility to and severity of asthma. We investigated the efficacy of human MSCs in high- vs. low-hMIF environments and the impact of MIF pre-licensing of MSCs using humanized MIF mice in a clinically relevant house dust mite (HDM) model of allergic asthma. MSCs significantly attenuated airway inflammation and airway remodeling in high-MIF-expressing CATT7 mice but not in CATT5 or wild-type littermates. Differences in efficacy were correlated with increased MSC retention in the lungs of CATT7 mice. MIF licensing potentiated MSC anti-inflammatory effects at a previously ineffective dose. Mechanistically, MIF binding to CD74 expressed on MSCs leads to upregulation of cyclooxygenase 2 (COX-2) expression. Blockade of CD74 or COX-2 function in MSCs prior to administration attenuated the efficacy of MIF-licensed MSCs in vivo. These findings suggest that MSC administration may be more efficacious in severe asthma patients with high MIF genotypes (CATT6/7/8).
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- allergic asthma
- cyclooxygenase
- house dust mite
- macrophage migration inhibitory factor
- mesenchymal stromal cells
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hawthorne, Ian J ...
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Dunbar, Hazel
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Tunstead, Courte ...
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Schorpp, Tamara
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Weiss, Daniel J.
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Enes, Sara Rolan ...
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visa fler...
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dos Santos, Clau ...
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Armstrong, Miche ...
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Donnelly, Seamas ...
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English, Karen
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Lungmedicin och ...
- Artiklar i publikationen
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Molecular Therap ...
- Av lärosätet
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Lunds universitet