T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction
Autor: | Pain, Mallory, Royer, Pierre-Joseph, Loy, Jennifer, Girardeau, Aurore, Tissot, A., Lacoste, P., Roux, A., Reynaud-Gaubert, M., Kessler, R., Mussot, S., Dromer, C., Brugiere, O., Mornex, J. -F., Guillemain, R., Dahan, M., Knoop, C., Botturi, Karine, Pison, C., Danger, R., Brouard, S., Magnan, Antoine, Consortium, COLT |
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Přispěvatelé: | unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CTG - Italcementi Group, Ciments CALCIA-Italcementi Group, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie, Nouvel Hôpital Civil Strasbourg, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Association Vaincre la Mucoviscidose, Agence de la Biomédecine, Fonds de Recherche en Santé Respiratoire, Fondation du Souffle, French government, Nantes Métropole and Région Pays de la Loire, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, ANR-10-IBHU-005, Agence Nationale de la Recherche, Association Gregory Lemarchal, Région Pays de La Loire, Institut de Recherche en Santé Respiratoire des Pays de la Loire, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Graft Rejection
Lung Diseases Male 0301 basic medicine Chemokine translational research/science T-Lymphocytes 030230 surgery Matrix metalloproteinase Chemokine receptor Postoperative Complications 0302 clinical medicine lung transplantation/pulmonology Risk Factors Transforming Growth Factor beta [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Immunology and Allergy Medicine Pharmacology (medical) Longitudinal Studies Epithelial cell differentiation biology Graft Survival Middle Aged Allografts Prognosis Matrix Metalloproteinase 9 Cytokines Female Lung Transplantation Adult Receptors CCR2 Bronchi Proinflammatory cytokine 03 medical and health sciences Immune system Humans Secretion Transplantation business.industry rejection: chronic Epithelial Cells Transforming growth factor beta 030104 developmental biology lung (allograft) function/dysfunction Chronic Disease Immunology biology.protein business bronchiolitis obliterans (BOS) Biomarkers Follow-Up Studies |
Zdroj: | American Journal of Transplantation American Journal of Transplantation, Wiley, 2017, 17 (6), pp.1502-1514. ⟨10.1111/ajt.14166⟩ American Journal of Transplantation, 2017, 17 (6), pp.1502-1514. ⟨10.1111/ajt.14166⟩ |
ISSN: | 1600-6135 1600-6143 |
Popis: | International audience; Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-beta. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-beta-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD. |
Databáze: | OpenAIRE |
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