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Ruwisch, J.* ; Cazes, A.* ; Leiber, L.M.* ; Borie, R.* ; Neubert, L.* ; Christian, L.* ; Thomas de Montpréville, V.* ; Szmul, A.* ; Moussa, F.* ; Verleden, S.E.* ; Gaedcke, S.* ; Hegermann, J.* ; Fuge, J.* ; Ballmaier, M.* ; Kamp, J.C.* ; Greer, M.* ; Braubach, P.* ; Werlein, C.* ; Ius, F.* ; Graalmann, T.* ; Aburahma, K.* ; De Sadeleer, L.J.* ; Egashira, R.* ; Ackermann, M.* ; Yamada, D.* ; Hoeper, M.M.* ; Falk, C.* ; Gottlieb, J.* ; Schiller, H. B. ; Vanaudenaerde, B.* ; Seeliger, B.* ; Debray, M.P.* ; Bernaudin, J.F.* ; Knudsen, L.* ; Bergot, E.* ; Jacob, J.* ; Mal, H.* ; Jonigk, D.* ; Dettmer, S.* ; Mordant, P.* ; Prasse, A.* ; Fadel, E.* ; Wuyts, W.A.* ; Crestani, B.* ; Kaminski, N.* ; Justet, A.* ; Schupp, J.C.*

The pleuroparenchymal fibroelastosis atlas reveals aberrant cell states and their zonation as an alternate roadmap to lung fibrosis.

Sci. Adv. 12:eaeb5967 (2026)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Pleuroparenchymal fibroelastosis (PPFE) is a progressive interstitial lung disease (ILD) with defining histology of intra-alveolar fibrosis with septal elastosis (AFE), suggesting unique cellular disease processes. Here, we present a binational single-nucleus RNA sequencing atlas of PPFE, based on explanted lungs from 40 patients. Immunofluorescence microscopy, RNA in situ hybridization, micro-computed tomography (CT), and hierarchical phase-contrast (HiP) synchrotron CT provided spatial context. We identify PPFE-associated adventitial and elastofibrotic fibroblasts as key drivers of elastotic remodeling within an inflammatory microenvironment, maintained by immune cells forming tertiary lymphoid structures. Spatial mapping reveals an intriguing zonation of AFE, maintained by intercellular circuits between PPFE-associated cell types. Comparative analysis with idiopathic pulmonary fibrosis highlights CTHRC1+ fibrotic fibroblasts and aberrant basaloid cells as conserved profibrotic cellular machinery mediating collagen deposition across ILDs. This integrative atlas defines the cellular landscape of PPFE and dissects elastotic from fibrotic remodeling, providing a molecular rationale for niche-specific therapeutic strategies.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 12, Issue: 19, Pages: , Article Number: eaeb5967 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)