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Inhibition of LTβR ...
Inhibition of LTβR signalling activates WNT-induced regeneration in lung
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- Conlon, Thomas M (author)
- Helmholtz Zentrum München
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John-Schuster, Gerrit (author)
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- Heide, Danijela (author)
- German Cancer Research Centre
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- Pfister, Dominik (author)
- German Cancer Research Centre
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- Lehmann, Mareike (author)
- Helmholtz Zentrum München
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- Hu, Yan (author)
- University of Northern Colorado
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Ertüz, Zeynep (author)
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- Lopez, Martin A (author)
- University of Liège Hospital
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Ansari, Meshal (author)
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Strunz, Maximilian (author)
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Mayr, Christoph (author)
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- Ciminieri, Chiara (author)
- University of Northern Colorado
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Costa, Rita (author)
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- Kohlhepp, Marlene Sophia (author)
- Charité - University Medicine Berlin
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- Guillot, Adrien (author)
- Charité - University Medicine Berlin
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Günes, Gizem (author)
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Jeridi, Aicha (author)
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- Funk, Maja C (author)
- German Cancer Research Centre
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Beroshvili, Giorgi (author)
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- Prokosch, Sandra (author)
- German Cancer Research Centre
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- Hetzer, Jenny (author)
- German Cancer Research Centre
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Verleden, Stijn E (author)
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- Alsafadi, Hani (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,Lung Bioengineering and Regeneration,Lund University Research Groups,German Center for Lung Research (DZL),Helmholtz Zentrum München
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- Lindner, Michael (author)
- German Center for Lung Research (DZL)
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Burgstaller, Gerald (author)
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- Becker, Lore (author)
- University of Warsaw
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- Irmler, Martin (author)
- University of Warsaw
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- Dudek, Michael (author)
- Technical University of Munich
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- Janzen, Jakob (author)
- German Cancer Research Centre
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- Goffin, Eric (author)
- University of Liège Hospital
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- Gosens, Reinoud (author)
- Hanze University of Applied Sciences
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- Knolle, Percy (author)
- Technical University of Munich
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- Pirotte, Bernard (author)
- University of Liège Hospital
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Stoeger, Tobias (author)
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- Beckers, Johannes (author)
- University of Warsaw
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- Wagner, Darcy (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,Lung Bioengineering and Regeneration,Lund University Research Groups,Helmholtz Zentrum München,German Center for Lung Research (DZL)
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- Singh, Indrabahadur (author)
- German Cancer Research Centre
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- Theis, Fabian J (author)
- Helmholtz Zentrum München
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- de Angelis, Martin Hrabé (author)
- University of Warsaw
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- O'Connor, Tracy (author)
- German Cancer Research Centre
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- Tacke, Frank (author)
- Charité - University Medicine Berlin
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- Boutros, Michael (author)
- German Cancer Research Centre
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- Dejardin, Emmanuel (author)
- University of Liège Hospital
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- Eickelberg, Oliver (author)
- University of Northern Colorado
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Schiller, Herbert B (author)
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Königshoff, Melanie (author)
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- Heikenwalder, Mathias (author)
- German Cancer Research Centre
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- Yildirim, Ali Önder (author)
- Helmholtz Zentrum München
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(creator_code:org_t)
- 2020-11-04
- 2020
- English 6 s.
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 588:7836, s. 151-156
- Related links:
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http://dx.doi.org/10...
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https://www.ncbi.nlm...
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Abstract
Subject headings
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- Lymphotoxin β-receptor (LTβR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTβR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTβR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTβR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTβR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTβR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTβR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFβ signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/β-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTβR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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Nature
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- By the author/editor
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Conlon, Thomas M
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John-Schuster, G ...
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Heide, Danijela
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Pfister, Dominik
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Lehmann, Mareike
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Hu, Yan
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show more...
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Ertüz, Zeynep
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Lopez, Martin A
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Ansari, Meshal
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Strunz, Maximili ...
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Mayr, Christoph
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Ciminieri, Chiar ...
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Costa, Rita
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Kohlhepp, Marlen ...
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Guillot, Adrien
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Günes, Gizem
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Jeridi, Aicha
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Funk, Maja C
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Beroshvili, Gior ...
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Prokosch, Sandra
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Hetzer, Jenny
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Verleden, Stijn ...
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Alsafadi, Hani
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Lindner, Michael
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Burgstaller, Ger ...
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Becker, Lore
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Irmler, Martin
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Dudek, Michael
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Janzen, Jakob
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Goffin, Eric
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Gosens, Reinoud
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Knolle, Percy
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Pirotte, Bernard
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Stoeger, Tobias
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Beckers, Johanne ...
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Wagner, Darcy
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Singh, Indrabaha ...
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Theis, Fabian J
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de Angelis, Mart ...
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O'Connor, Tracy
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Tacke, Frank
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Boutros, Michael
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Dejardin, Emmanu ...
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Eickelberg, Oliv ...
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Schiller, Herber ...
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Königshoff, Mela ...
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Heikenwalder, Ma ...
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Yildirim, Ali Ön ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Respiratory Medi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Nature
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Lund University