Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G
One of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immuno...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/8250584 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850166828610879488 |
|---|---|
| author | Catherine A. Lombard Gwenaëlle Sana Joël LeMaoult Mehdi Najar Joachim Ravau Floriane André Fatima Bouhtit Marina Daouya Maria Loustau Mustapha Najimi Laurence Lagneaux Edgardo D. Carosella Etienne M. Sokal |
| author_facet | Catherine A. Lombard Gwenaëlle Sana Joël LeMaoult Mehdi Najar Joachim Ravau Floriane André Fatima Bouhtit Marina Daouya Maria Loustau Mustapha Najimi Laurence Lagneaux Edgardo D. Carosella Etienne M. Sokal |
| author_sort | Catherine A. Lombard |
| collection | DOAJ |
| description | One of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immunosuppressive properties of human hepatocytes and adult-derived human liver stem/progenitor cells (ADHLSCs), as well as the potential involvement of the immunomodulatory molecule HLA-G. We demonstrated that both cell types were capable of inhibiting the proliferative response of PBMCs to an allogenic stimulus and that the immune inhibitory potential of ADHLSCs, although lower than that of hepatocytes, increased after hepatogenic differentiation. We demonstrated that liver cells express HLA-G and that the immune inhibition pattern was clearly associated to its expression. Interestingly, HLA-G expression increased after the third step of differentiation, wherein oncostatin M (OSM) was added. A 48 hr treatment with OSM was sufficient to induce HLA-G expression in ADHLSCs and result in immune inhibition. Surprisingly, blocking HLA-G partially reversed the immune inhibition mediated by hepatocytes and differentiated ADHLSCs, but not that of undifferentiated ADHLSCs, suggesting that additional immune inhibitory mechanisms may be used by these cells. In conclusion, we demonstrated that both hepatocytes and ADHLSCs present immunomodulatory properties mediated, at least in part, through HLA-G, which can be upregulated following hepatogenic differentiation or liver cell pretreatment with OSM. These observations open up new perspectives for the induction of tolerance following LCT and for potential therapeutic applications of these liver cells. |
| format | Article |
| id | doaj-art-dab643f5b2ef41f79d4dcdc7b9bc1b97 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-dab643f5b2ef41f79d4dcdc7b9bc1b972025-08-20T02:21:20ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/82505848250584Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-GCatherine A. Lombard0Gwenaëlle Sana1Joël LeMaoult2Mehdi Najar3Joachim Ravau4Floriane André5Fatima Bouhtit6Marina Daouya7Maria Loustau8Mustapha Najimi9Laurence Lagneaux10Edgardo D. Carosella11Etienne M. Sokal12Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumService de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Avenue Claude Vellefaux 1, 75010 Paris, FranceOsteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), 900 rue Saint-Denis, R11.424, Montreal, QC, H2X 0A9, CanadaLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumLaboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Campus Erasme, Brussels, BelgiumService de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Avenue Claude Vellefaux 1, 75010 Paris, FranceService de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Avenue Claude Vellefaux 1, 75010 Paris, FranceLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumLaboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Campus Erasme, Brussels, BelgiumService de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Avenue Claude Vellefaux 1, 75010 Paris, FranceLaboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain & Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, BelgiumOne of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immunosuppressive properties of human hepatocytes and adult-derived human liver stem/progenitor cells (ADHLSCs), as well as the potential involvement of the immunomodulatory molecule HLA-G. We demonstrated that both cell types were capable of inhibiting the proliferative response of PBMCs to an allogenic stimulus and that the immune inhibitory potential of ADHLSCs, although lower than that of hepatocytes, increased after hepatogenic differentiation. We demonstrated that liver cells express HLA-G and that the immune inhibition pattern was clearly associated to its expression. Interestingly, HLA-G expression increased after the third step of differentiation, wherein oncostatin M (OSM) was added. A 48 hr treatment with OSM was sufficient to induce HLA-G expression in ADHLSCs and result in immune inhibition. Surprisingly, blocking HLA-G partially reversed the immune inhibition mediated by hepatocytes and differentiated ADHLSCs, but not that of undifferentiated ADHLSCs, suggesting that additional immune inhibitory mechanisms may be used by these cells. In conclusion, we demonstrated that both hepatocytes and ADHLSCs present immunomodulatory properties mediated, at least in part, through HLA-G, which can be upregulated following hepatogenic differentiation or liver cell pretreatment with OSM. These observations open up new perspectives for the induction of tolerance following LCT and for potential therapeutic applications of these liver cells.http://dx.doi.org/10.1155/2019/8250584 |
| spellingShingle | Catherine A. Lombard Gwenaëlle Sana Joël LeMaoult Mehdi Najar Joachim Ravau Floriane André Fatima Bouhtit Marina Daouya Maria Loustau Mustapha Najimi Laurence Lagneaux Edgardo D. Carosella Etienne M. Sokal Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G Journal of Immunology Research |
| title | Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G |
| title_full | Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G |
| title_fullStr | Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G |
| title_full_unstemmed | Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G |
| title_short | Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display In Vitro Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G |
| title_sort | human hepatocytes and differentiated adult derived human liver stem progenitor cells display in vitro immunosuppressive properties mediated at least in part through the nonclassical hla class i molecule hla g |
| url | http://dx.doi.org/10.1155/2019/8250584 |
| work_keys_str_mv | AT catherinealombard humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT gwenaellesana humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT joellemaoult humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT mehdinajar humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT joachimravau humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT florianeandre humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT fatimabouhtit humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT marinadaouya humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT marialoustau humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT mustaphanajimi humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT laurencelagneaux humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT edgardodcarosella humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag AT etiennemsokal humanhepatocytesanddifferentiatedadultderivedhumanliverstemprogenitorcellsdisplayinvitroimmunosuppressivepropertiesmediatedatleastinpartthroughthenonclassicalhlaclassimoleculehlag |