Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy
Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00643/full |
| _version_ | 1828911458625257472 |
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| author | María Iglesias-Escudero David Sansegundo-Arribas David Sansegundo-Arribas Paloma Riquelme David Merino-Fernández Sandra Guiral-Foz Sandra Guiral-Foz Carmen Pérez Rosalia Valero Rosalia Valero Juan Carlos Ruiz Juan Carlos Ruiz Emilio Rodrigo Emilio Rodrigo Patricia Lamadrid-Perojo James A. Hutchinson Jordi Ochando Jordi Ochando Marcos López-Hoyos Marcos López-Hoyos |
| author_facet | María Iglesias-Escudero David Sansegundo-Arribas David Sansegundo-Arribas Paloma Riquelme David Merino-Fernández Sandra Guiral-Foz Sandra Guiral-Foz Carmen Pérez Rosalia Valero Rosalia Valero Juan Carlos Ruiz Juan Carlos Ruiz Emilio Rodrigo Emilio Rodrigo Patricia Lamadrid-Perojo James A. Hutchinson Jordi Ochando Jordi Ochando Marcos López-Hoyos Marcos López-Hoyos |
| author_sort | María Iglesias-Escudero |
| collection | DOAJ |
| description | Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce. We evaluated the phenotype and function of different MDSCs subsets in 38 kidney transplant recipients (KTRs) at different time points. Our data indicate that monocytic MDSCs (Mo-MDSC) increase in KTR at 6 and 12 months posttransplantation. On the contrary, the percentages of polymorphonuclear MDSC (PMN-MDSC) and early-stage MDSC (e-MDSC) are not significantly increased. We evaluated the immunosuppressive activity of Mo-MDSC in KTR and confirmed their ability to increase regulatory T cells (Treg) in vitro. Interestingly, when we compared the ability of Mo-MDSC to suppress T cell proliferation, we observed that tacrolimus, but not rapamycin-treated KTR, was able to inhibit CD4+ T cell proliferation in vitro. This indicates that, although mTOR inhibitors are widely regarded as supportive of regulatory responses, rapamycin may impair Mo-MDSC function, and suggests that the choice of immunosuppressive therapy may determine the tolerogenic pathway and participating immune cells that promote organ transplant acceptance in KTR. |
| first_indexed | 2024-12-13T19:03:28Z |
| format | Article |
| id | doaj.art-af04e9aa6d044ea49755131b3716c429 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T19:03:28Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-af04e9aa6d044ea49755131b3716c4292022-12-21T23:34:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00643488809Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance ImmunotherapyMaría Iglesias-Escudero0David Sansegundo-Arribas1David Sansegundo-Arribas2Paloma Riquelme3David Merino-Fernández4Sandra Guiral-Foz5Sandra Guiral-Foz6Carmen Pérez7Rosalia Valero8Rosalia Valero9Juan Carlos Ruiz10Juan Carlos Ruiz11Emilio Rodrigo12Emilio Rodrigo13Patricia Lamadrid-Perojo14James A. Hutchinson15Jordi Ochando16Jordi Ochando17Marcos López-Hoyos18Marcos López-Hoyos19Transplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Immunology, University Hospital Marqués de Valdecilla, Santander, SpainSection of Experimental Surgery, Department of Surgery, University Hospital of Regensburg, Regensburg, GermanyTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Immunology, University Hospital Marqués de Valdecilla, Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Nephrology, University Hospital Marqués de Valdecilla, Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Nephrology, University Hospital Marqués de Valdecilla, Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Nephrology, University Hospital Marqués de Valdecilla, Santander, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainSection of Experimental Surgery, Department of Surgery, University Hospital of Regensburg, Regensburg, GermanyDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesImmunología de Trasplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainTransplantation and Autoimmunity Group, Marqués de Valdecilla Health Research Institute (IDIVAL)Santander, SpainDepartment of Immunology, University Hospital Marqués de Valdecilla, Santander, SpainMyeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce. We evaluated the phenotype and function of different MDSCs subsets in 38 kidney transplant recipients (KTRs) at different time points. Our data indicate that monocytic MDSCs (Mo-MDSC) increase in KTR at 6 and 12 months posttransplantation. On the contrary, the percentages of polymorphonuclear MDSC (PMN-MDSC) and early-stage MDSC (e-MDSC) are not significantly increased. We evaluated the immunosuppressive activity of Mo-MDSC in KTR and confirmed their ability to increase regulatory T cells (Treg) in vitro. Interestingly, when we compared the ability of Mo-MDSC to suppress T cell proliferation, we observed that tacrolimus, but not rapamycin-treated KTR, was able to inhibit CD4+ T cell proliferation in vitro. This indicates that, although mTOR inhibitors are widely regarded as supportive of regulatory responses, rapamycin may impair Mo-MDSC function, and suggests that the choice of immunosuppressive therapy may determine the tolerogenic pathway and participating immune cells that promote organ transplant acceptance in KTR.https://www.frontiersin.org/article/10.3389/fimmu.2020.00643/fullkidney transplantationmTOR inhibitionmyeloid-derived suppressor cellstacrolimusimmunosuppression |
| spellingShingle | María Iglesias-Escudero David Sansegundo-Arribas David Sansegundo-Arribas Paloma Riquelme David Merino-Fernández Sandra Guiral-Foz Sandra Guiral-Foz Carmen Pérez Rosalia Valero Rosalia Valero Juan Carlos Ruiz Juan Carlos Ruiz Emilio Rodrigo Emilio Rodrigo Patricia Lamadrid-Perojo James A. Hutchinson Jordi Ochando Jordi Ochando Marcos López-Hoyos Marcos López-Hoyos Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy Frontiers in Immunology kidney transplantation mTOR inhibition myeloid-derived suppressor cells tacrolimus immunosuppression |
| title | Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy |
| title_full | Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy |
| title_fullStr | Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy |
| title_full_unstemmed | Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy |
| title_short | Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy |
| title_sort | myeloid derived suppressor cells in kidney transplant recipients and the effect of maintenance immunotherapy |
| topic | kidney transplantation mTOR inhibition myeloid-derived suppressor cells tacrolimus immunosuppression |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00643/full |
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