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
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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