Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation
Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capaci...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/5924 |
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| author | Benoit R. Gauthier Diana Rubio-Contreras Juan Carlos Gómez-Rosado Luis Cristobal Capitán-Morales Abdelkrim Hmadcha Bernat Soria Christian Claude Lachaud |
| author_facet | Benoit R. Gauthier Diana Rubio-Contreras Juan Carlos Gómez-Rosado Luis Cristobal Capitán-Morales Abdelkrim Hmadcha Bernat Soria Christian Claude Lachaud |
| author_sort | Benoit R. Gauthier |
| collection | DOAJ |
| description | Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-β and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19<sup>+</sup>/CD25<sup>+</sup> B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFβ and activin signaling pathways, or with a monoclonal antibody against the TGFβ1, β2, and β3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators. |
| first_indexed | 2024-03-10T01:17:29Z |
| format | Article |
| id | doaj.art-cca9d570280f4f41a660d260cca58406 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:17:29Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cca9d570280f4f41a660d260cca584062023-11-23T14:06:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311592410.3390/ijms23115924Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell ActivationBenoit R. Gauthier0Diana Rubio-Contreras1Juan Carlos Gómez-Rosado2Luis Cristobal Capitán-Morales3Abdelkrim Hmadcha4Bernat Soria5Christian Claude Lachaud6Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, and Departamento de Genética, Universidad de Sevilla, 41013 Seville, SpainUnidad de Gestión Clínica de Cirugía General y Digestiva, Hospital Universitario Virgen Macarena, Avda. Dr Fedriani s/n, 41009 Sevilla, SpainUnidad de Gestión Clínica de Cirugía General y Digestiva, Hospital Universitario Virgen Macarena, Avda. Dr Fedriani s/n, 41009 Sevilla, SpainBiomedical Research Network on Diabetes and Related Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, 28029 Madrid, SpainBiomedical Research Network on Diabetes and Related Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, 28029 Madrid, SpainAndalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, SpainMesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-β and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19<sup>+</sup>/CD25<sup>+</sup> B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFβ and activin signaling pathways, or with a monoclonal antibody against the TGFβ1, β2, and β3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators.https://www.mdpi.com/1422-0067/23/11/5924mesothelial cellsadult stem cellslymphocytesmacrophagesimmunosuppressionimmunomodulation |
| spellingShingle | Benoit R. Gauthier Diana Rubio-Contreras Juan Carlos Gómez-Rosado Luis Cristobal Capitán-Morales Abdelkrim Hmadcha Bernat Soria Christian Claude Lachaud Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation International Journal of Molecular Sciences mesothelial cells adult stem cells lymphocytes macrophages immunosuppression immunomodulation |
| title | Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation |
| title_full | Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation |
| title_fullStr | Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation |
| title_full_unstemmed | Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation |
| title_short | Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation |
| title_sort | human omental mesothelial cells impart an immunomodulatory landscape impeding b and t cell activation |
| topic | mesothelial cells adult stem cells lymphocytes macrophages immunosuppression immunomodulation |
| url | https://www.mdpi.com/1422-0067/23/11/5924 |
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