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Schiller, H. B. ; Mayr, C.H. ; Leuschner, G. ; Strunz, M. ; Staab-Weijnitz, C.A. ; Preisendörfer, S. ; Eckes, B.* ; Moinzadeh, P.* ; Krieg, T.* ; Schwartz, D.A.* ; Hatz, R.A.* ; Behr, J.* ; Mann, M.* ; Eickelberg, O.

Deep proteome profiling reveals common prevalence of MZB1-positive plasma B cells in human lung and skin fibrosis.

Am. J. Respir. Crit. Care Med. 196, 1298-1310 (2017)
Verlagsversion Postprint Forschungsdaten Forschungsdaten DOI PMC
Open Access Green
RATIONALE: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. OBJECTIVES: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across endstage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. METHODS: We collected samples of ILD tissue (n=45) and healthy donor controls (n=10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n=6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. MEASUREMENTS AND MAIN RESULTS: We determined the abundance of >7900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteome comparison of lung and skin fibrosis identified a common upregulation of MZB1, the expression of which identified MZB1+/CD38+/CD138+/CD27+/CD45-/CD20- plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG, and negatively with diffusing capacity of the lung for carbon monoxide (DLCO). CONCLUSIONS: Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1+ plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis (IPF).
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Fibrosis, Proteomics, Ild, Localized Scleroderma (morphea), Mzb1, Autoimmunity; Idiopathic Pulmonary-fibrosis; Oligomeric Matrix Protein; Key Regulator; Tissue; Mice; Secretion; Repair; Differentiation; Identification; Regeneration
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Zeitschrift American Journal of Respiratory and Critical Care Medicine
Quellenangaben Band: 196, Heft: 10, Seiten: 1298-1310 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Verlagsort New York
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) German Center for Lung Research (DZL)
Institute of Lung Health and Immunity (LHI)