Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity
Abstract Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40367-3 |
| _version_ | 1797559537708826624 |
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| author | Suguru Tamura Hajime Ishiguro Tatsuya Suwabe Takayuki Katagiri Kaori Cho Kyoko Fuse Yasuhiko Shibasaki Tadahisa Mikami Takero Shindo Hiroshi Kitagawa Michihiro Igarashi Hirohito Sone Masayoshi Masuko Takashi Ushiki |
| author_facet | Suguru Tamura Hajime Ishiguro Tatsuya Suwabe Takayuki Katagiri Kaori Cho Kyoko Fuse Yasuhiko Shibasaki Tadahisa Mikami Takero Shindo Hiroshi Kitagawa Michihiro Igarashi Hirohito Sone Masayoshi Masuko Takashi Ushiki |
| author_sort | Suguru Tamura |
| collection | DOAJ |
| description | Abstract Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation. |
| first_indexed | 2024-03-10T17:46:48Z |
| format | Article |
| id | doaj.art-505d011b3c3b4c36bbbe1188c6e5bb1a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:46:48Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-505d011b3c3b4c36bbbe1188c6e5bb1a2023-11-20T09:29:13ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-40367-3Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activitySuguru Tamura0Hajime Ishiguro1Tatsuya Suwabe2Takayuki Katagiri3Kaori Cho4Kyoko Fuse5Yasuhiko Shibasaki6Tadahisa Mikami7Takero Shindo8Hiroshi Kitagawa9Michihiro Igarashi10Hirohito Sone11Masayoshi Masuko12Takashi Ushiki13Department of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineLaboratory of Biochemistry, Kobe Pharmaceutical UniversityDepartment of Hematology/Oncology, Kyoto University Graduate School of MedicineLaboratory of Biochemistry, Kobe Pharmaceutical UniversityDepartment of Neurochemistry and Molecular Cell Biology, Niigata University Graduate School of Medical and Dental SciencesDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineDepartment of Hematology, Niigata University Faculty of MedicineAbstract Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.https://doi.org/10.1038/s41598-023-40367-3 |
| spellingShingle | Suguru Tamura Hajime Ishiguro Tatsuya Suwabe Takayuki Katagiri Kaori Cho Kyoko Fuse Yasuhiko Shibasaki Tadahisa Mikami Takero Shindo Hiroshi Kitagawa Michihiro Igarashi Hirohito Sone Masayoshi Masuko Takashi Ushiki Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity Scientific Reports |
| title | Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity |
| title_full | Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity |
| title_fullStr | Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity |
| title_full_unstemmed | Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity |
| title_short | Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity |
| title_sort | genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic gvhd via suppression of t cell activity |
| url | https://doi.org/10.1038/s41598-023-40367-3 |
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