Lung immunoglobulin A immunity dysregulation in cystic fibrosis
Background: In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396420303509 |
| _version_ | 1818203023363538944 |
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| author | Amandine M. Collin Marylène Lecocq Sabrina Noel Bruno Detry François M. Carlier Frank Aboubakar Nana Caroline Bouzin Teresinha Leal Marjorie Vermeersch Virginia De Rose Lucile Regard Clémence Martin Pierre-Régis Burgel Delphine Hoton Stijn Verleden Antoine Froidure Charles Pilette Sophie Gohy |
| author_facet | Amandine M. Collin Marylène Lecocq Sabrina Noel Bruno Detry François M. Carlier Frank Aboubakar Nana Caroline Bouzin Teresinha Leal Marjorie Vermeersch Virginia De Rose Lucile Regard Clémence Martin Pierre-Régis Burgel Delphine Hoton Stijn Verleden Antoine Froidure Charles Pilette Sophie Gohy |
| author_sort | Amandine M. Collin |
| collection | DOAJ |
| description | Background: In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d-)IgA and represents a major defence through neutralisation of inhaled pathogens like Pseudomonas aeruginosa (Pa). Methods: Human lung tissue (n = 74), human sputum (n = 118), primary human bronchial epithelial cells (HBEC) (cultured in air-liquid interface) (n = 19) and mouse lung tissue and bronchoalveolar lavage were studied for pIgR expression, IgA secretion and regulation. Findings: Increased epithelial pIgR immunostaining was observed in CF lung explants, associated with more IgA-producing plasma cells, sputum and serum IgA, especially Pa-specific IgA. In contrast, pIgR and IgA transport were downregulated in F508del mice, CFTR-inhibited HBEC, and CF HBEC. Moreover, the unfolded protein response (UPR) due to F508del mutation, inhibited IgA transport in Calu-3 cells. Conversely, pIgR expression and IgA secretion were strongly upregulated following Pa lung infection in control and F508del mice, through an inflammatory host response involving interleukin-17. Interpretation: A complex regulation of IgA secretion occurs in the CF lung, UPR induced by CFTR mutation/dysfunction inhibiting d-IgA transcytosis, and Pa infection unexpectedly unleashing this secretory defence mechanism. Funding: This work was supported by the Forton's grant of the King Baudouin's Foundation, Belgium, the Fondazione Ricerca Fibrosi Cistica, Italy, and the Fonds National de la Recherche Scientifique, Belgium. |
| first_indexed | 2024-12-12T03:18:45Z |
| format | Article |
| id | doaj.art-06b07803ab7e44948551ce1de9ddf19f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T03:18:45Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-06b07803ab7e44948551ce1de9ddf19f2022-12-22T00:40:13ZengElsevierEBioMedicine2352-39642020-10-0160102974Lung immunoglobulin A immunity dysregulation in cystic fibrosisAmandine M. Collin0Marylène Lecocq1Sabrina Noel2Bruno Detry3François M. Carlier4Frank Aboubakar Nana5Caroline Bouzin6Teresinha Leal7Marjorie Vermeersch8Virginia De Rose9Lucile Regard10Clémence Martin11Pierre-Régis Burgel12Delphine Hoton13Stijn Verleden14Antoine Froidure15Charles Pilette16Sophie Gohy17Pole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumLouvain Centre for Toxicology and Applied Pharmacology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumImaging Platform, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumLouvain Centre for Toxicology and Applied Pharmacology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, BelgiumCenter for Microscopy and Molecular Imaging, Université libre de Bruxelles (ULB), Gosselies, BelgiumDepartment of Clinical and Biological Sciences, University of Torino, A.O.U. S. Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Torino, ItalyService de pneumologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; Institut Cochin, Université de Paris, Inserm U1016, Paris, FranceService de pneumologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; Institut Cochin, Université de Paris, Inserm U1016, Paris, FranceService de pneumologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; Institut Cochin, Université de Paris, Inserm U1016, Paris, FranceDepartment of Pathology, Cliniques universitaires Saint-Luc, Brussels, BelgiumLung Transplant Unit, Division of Respiratory Disease, Department of chronic disease, metabolism and aging, Katholieke Universiteit Leuven, Leuven, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Pneumology, Cliniques universitaires Saint-Luc, Brussels, BelgiumPole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Corresponding author.Pole of Pneumology, ENT and Dermatology, Institute of Experimental & Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Centre de référence pour la mucoviscidose, Cliniques universitaires Saint-Luc, Brussels, Belgium; Corresponding author.Background: In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d-)IgA and represents a major defence through neutralisation of inhaled pathogens like Pseudomonas aeruginosa (Pa). Methods: Human lung tissue (n = 74), human sputum (n = 118), primary human bronchial epithelial cells (HBEC) (cultured in air-liquid interface) (n = 19) and mouse lung tissue and bronchoalveolar lavage were studied for pIgR expression, IgA secretion and regulation. Findings: Increased epithelial pIgR immunostaining was observed in CF lung explants, associated with more IgA-producing plasma cells, sputum and serum IgA, especially Pa-specific IgA. In contrast, pIgR and IgA transport were downregulated in F508del mice, CFTR-inhibited HBEC, and CF HBEC. Moreover, the unfolded protein response (UPR) due to F508del mutation, inhibited IgA transport in Calu-3 cells. Conversely, pIgR expression and IgA secretion were strongly upregulated following Pa lung infection in control and F508del mice, through an inflammatory host response involving interleukin-17. Interpretation: A complex regulation of IgA secretion occurs in the CF lung, UPR induced by CFTR mutation/dysfunction inhibiting d-IgA transcytosis, and Pa infection unexpectedly unleashing this secretory defence mechanism. Funding: This work was supported by the Forton's grant of the King Baudouin's Foundation, Belgium, the Fondazione Ricerca Fibrosi Cistica, Italy, and the Fonds National de la Recherche Scientifique, Belgium.http://www.sciencedirect.com/science/article/pii/S2352396420303509Cystic fibrosisImmunoglobulin ALung mucosal immunityInfectionEndoplasmic reticulum stress |
| spellingShingle | Amandine M. Collin Marylène Lecocq Sabrina Noel Bruno Detry François M. Carlier Frank Aboubakar Nana Caroline Bouzin Teresinha Leal Marjorie Vermeersch Virginia De Rose Lucile Regard Clémence Martin Pierre-Régis Burgel Delphine Hoton Stijn Verleden Antoine Froidure Charles Pilette Sophie Gohy Lung immunoglobulin A immunity dysregulation in cystic fibrosis EBioMedicine Cystic fibrosis Immunoglobulin A Lung mucosal immunity Infection Endoplasmic reticulum stress |
| title | Lung immunoglobulin A immunity dysregulation in cystic fibrosis |
| title_full | Lung immunoglobulin A immunity dysregulation in cystic fibrosis |
| title_fullStr | Lung immunoglobulin A immunity dysregulation in cystic fibrosis |
| title_full_unstemmed | Lung immunoglobulin A immunity dysregulation in cystic fibrosis |
| title_short | Lung immunoglobulin A immunity dysregulation in cystic fibrosis |
| title_sort | lung immunoglobulin a immunity dysregulation in cystic fibrosis |
| topic | Cystic fibrosis Immunoglobulin A Lung mucosal immunity Infection Endoplasmic reticulum stress |
| url | http://www.sciencedirect.com/science/article/pii/S2352396420303509 |
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