Immunoregulatory effects of RGMb in gut inflammation
Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.960329/full |
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| author | Magdiel Pérez-Cruz Bettina P. Iliopoulou Katie Hsu Hsin-Hsu Wu Tom Erkers Kavya Swaminathan Sai-Wen Tang Cameron S. Bader Neeraja Kambham Bryan Xie Rosemarie H. Dekruyff Gordon J. Freeman Everett Meyer |
| author_facet | Magdiel Pérez-Cruz Bettina P. Iliopoulou Katie Hsu Hsin-Hsu Wu Tom Erkers Kavya Swaminathan Sai-Wen Tang Cameron S. Bader Neeraja Kambham Bryan Xie Rosemarie H. Dekruyff Gordon J. Freeman Everett Meyer |
| author_sort | Magdiel Pérez-Cruz |
| collection | DOAJ |
| description | Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice. |
| first_indexed | 2024-04-11T22:54:22Z |
| format | Article |
| id | doaj.art-52d810967da849ec81e0eb878c3f5f63 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T22:54:22Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-52d810967da849ec81e0eb878c3f5f632022-12-22T03:58:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.960329960329Immunoregulatory effects of RGMb in gut inflammationMagdiel Pérez-Cruz0Bettina P. Iliopoulou1Katie Hsu2Hsin-Hsu Wu3Tom Erkers4Kavya Swaminathan5Sai-Wen Tang6Cameron S. Bader7Neeraja Kambham8Bryan Xie9Rosemarie H. Dekruyff10Gordon J. Freeman11Everett Meyer12Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Developmental biology, Stanford University School of Medicine, Stanford, CA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United StatesDivision of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United StatesGraft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice.https://www.frontiersin.org/articles/10.3389/fimmu.2022.960329/fullRGMBGvHDgut inflammationcolitisimmunoregulation |
| spellingShingle | Magdiel Pérez-Cruz Bettina P. Iliopoulou Katie Hsu Hsin-Hsu Wu Tom Erkers Kavya Swaminathan Sai-Wen Tang Cameron S. Bader Neeraja Kambham Bryan Xie Rosemarie H. Dekruyff Gordon J. Freeman Everett Meyer Immunoregulatory effects of RGMb in gut inflammation Frontiers in Immunology RGMB GvHD gut inflammation colitis immunoregulation |
| title | Immunoregulatory effects of RGMb in gut inflammation |
| title_full | Immunoregulatory effects of RGMb in gut inflammation |
| title_fullStr | Immunoregulatory effects of RGMb in gut inflammation |
| title_full_unstemmed | Immunoregulatory effects of RGMb in gut inflammation |
| title_short | Immunoregulatory effects of RGMb in gut inflammation |
| title_sort | immunoregulatory effects of rgmb in gut inflammation |
| topic | RGMB GvHD gut inflammation colitis immunoregulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.960329/full |
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