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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
Author(s) -
Pain M.,
Royer P.J.,
Loy J.,
Girardeau A.,
Tissot A.,
Lacoste P.,
Roux A.,
ReynaudGaubert M.,
Kessler R.,
Mussot S.,
Dromer C.,
Brugière O.,
Mornex J.F.,
Guillemain R.,
Dahan M.,
Knoop C.,
Botturi K.,
Pison C.,
Danger R.,
Brouard S.,
Magnan A.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14166
Subject(s) - chemokine , medicine , bronchiolitis obliterans , lung transplantation , immunology , lung , matrix metalloproteinase , chemokine receptor , inflammation , cancer research , pathology
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) ‐β. 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 ‐β–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 .