LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice
Despite significant therapeutic advances, graft-versus-host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.670776/full |
| _version_ | 1830179397718507520 |
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| author | Mohamed Jeljeli Mohamed Jeljeli Charlotte Chêne Sandrine Chouzenoux Marine Thomas Benjamin Segain Ludivine Doridot Carole Nicco Frédéric Batteux Frédéric Batteux |
| author_facet | Mohamed Jeljeli Mohamed Jeljeli Charlotte Chêne Sandrine Chouzenoux Marine Thomas Benjamin Segain Ludivine Doridot Carole Nicco Frédéric Batteux Frédéric Batteux |
| author_sort | Mohamed Jeljeli |
| collection | DOAJ |
| description | Despite significant therapeutic advances, graft-versus-host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmunity in chronic forms. A multitude of cell therapy approaches, including infusion of myeloid cells, has been proposed to prevent GvHD through tolerance induction but yielded variable results. Myeloid cells like macrophages can be reprogrammed to develop adaptive-like features following antigenic challenge to reinforce or inhibit a subsequent immune response; a phenomenon termed ‘trained immunity’. Here we report that, whereas LPSlow-trained macrophages elicit a suppressor effect on allogeneic T cell proliferation and function in vitro in an IL-10-dependent manner, Bacille Calmette et Guérin (BCG)-trained macrophages exert an opposite effect. In a murine model of sclerodermatous chronic GvHD, LPSlow-trained macrophages attenuate clinical signs of GvHD with significant effects on T cell phenotype and function, autoantibodies production, and tissue fibrosis. Furthermore, infusion of LPSlow-macrophages significantly improves survival in mice with acute GvHD. Importantly, we also provide evidence that LPSlow-macrophages do not accelerate A20-lymphoma tumor growth, which is significantly reduced upon transfer of BCG-macrophages. Collectively, these data indicate that macrophages can be trained to significantly inhibit in vitro and in vivo allo-reactive T cell proliferation without exhibiting pro-tumoral effect, thereby opening the way to promising clinical applications. |
| first_indexed | 2024-12-17T19:58:42Z |
| format | Article |
| id | doaj.art-8d4489458cec47d9bd96898929fd30a9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T19:58:42Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8d4489458cec47d9bd96898929fd30a92022-12-21T21:34:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.670776670776LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in MiceMohamed Jeljeli0Mohamed Jeljeli1Charlotte Chêne2Sandrine Chouzenoux3Marine Thomas4Benjamin Segain5Ludivine Doridot6Carole Nicco7Frédéric Batteux8Frédéric Batteux9Département 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceUniversité de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d’immunologie biologique, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceDépartement 3I «Infection, Immunité et Inflammation», Institut Cochin, INSERM U1016, Université de Paris, Paris, FranceUniversité de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d’immunologie biologique, Paris, FranceDespite significant therapeutic advances, graft-versus-host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmunity in chronic forms. A multitude of cell therapy approaches, including infusion of myeloid cells, has been proposed to prevent GvHD through tolerance induction but yielded variable results. Myeloid cells like macrophages can be reprogrammed to develop adaptive-like features following antigenic challenge to reinforce or inhibit a subsequent immune response; a phenomenon termed ‘trained immunity’. Here we report that, whereas LPSlow-trained macrophages elicit a suppressor effect on allogeneic T cell proliferation and function in vitro in an IL-10-dependent manner, Bacille Calmette et Guérin (BCG)-trained macrophages exert an opposite effect. In a murine model of sclerodermatous chronic GvHD, LPSlow-trained macrophages attenuate clinical signs of GvHD with significant effects on T cell phenotype and function, autoantibodies production, and tissue fibrosis. Furthermore, infusion of LPSlow-macrophages significantly improves survival in mice with acute GvHD. Importantly, we also provide evidence that LPSlow-macrophages do not accelerate A20-lymphoma tumor growth, which is significantly reduced upon transfer of BCG-macrophages. Collectively, these data indicate that macrophages can be trained to significantly inhibit in vitro and in vivo allo-reactive T cell proliferation without exhibiting pro-tumoral effect, thereby opening the way to promising clinical applications.https://www.frontiersin.org/articles/10.3389/fimmu.2021.670776/fullmacrophagestrained immunitygraft-versus-host diseasealloimmunityinflammationanti-tumoral action |
| spellingShingle | Mohamed Jeljeli Mohamed Jeljeli Charlotte Chêne Sandrine Chouzenoux Marine Thomas Benjamin Segain Ludivine Doridot Carole Nicco Frédéric Batteux Frédéric Batteux LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice Frontiers in Immunology macrophages trained immunity graft-versus-host disease alloimmunity inflammation anti-tumoral action |
| title | LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice |
| title_full | LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice |
| title_fullStr | LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice |
| title_full_unstemmed | LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice |
| title_short | LPSlow-Macrophages Alleviate the Outcome of Graft-Versus-Host Disease Without Aggravating Lymphoma Growth in Mice |
| title_sort | lpslow macrophages alleviate the outcome of graft versus host disease without aggravating lymphoma growth in mice |
| topic | macrophages trained immunity graft-versus-host disease alloimmunity inflammation anti-tumoral action |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.670776/full |
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