Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model
Abstract We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-lin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-08949-9 |
| _version_ | 1818356596313423872 |
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| author | Jun Zhu Takenori Inomata Masahiro Nakamura Keiichi Fujimoto Yasutsugu Akasaki Kenta Fujio Ai Yanagawa Koichiro Uchida Jaemyoung Sung Naoko Negishi Ken Nagino Yuichi Okumura Maria Miura Hurramhon Shokirova Mizu Kuwahara Kunihiko Hirosawa Akie Midorikawa-Inomata Atsuko Eguchi Tianxiang Huang Hideo Yagita Sonoko Habu Ko Okumura Akira Murakami |
| author_facet | Jun Zhu Takenori Inomata Masahiro Nakamura Keiichi Fujimoto Yasutsugu Akasaki Kenta Fujio Ai Yanagawa Koichiro Uchida Jaemyoung Sung Naoko Negishi Ken Nagino Yuichi Okumura Maria Miura Hurramhon Shokirova Mizu Kuwahara Kunihiko Hirosawa Akie Midorikawa-Inomata Atsuko Eguchi Tianxiang Huang Hideo Yagita Sonoko Habu Ko Okumura Akira Murakami |
| author_sort | Jun Zhu |
| collection | DOAJ |
| description | Abstract We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-linked immunosorbent assay. Interferon (IFN)-γ-producing CD4+ T cell frequencies in the MLR were assessed using flow cytometry. In vivo, high-risk corneal allograft survival and IFN-γ-producing CD4+ T cell frequencies in corneal grafts were assessed with intraperitoneal injection of anti-CD80/86 antibodies compared to phosphate-buffered saline (PBS). RNA-sequencing was performed on corneal grafts 2 weeks post-transplantation. Anti-CD80/86 antibodies significantly decreased T-cell proliferation, IFN-γ+-producing CD4+ T cell frequencies, and IFN-γ, interleukin (IL)-1β, IL-2, IL-10, and tumor necrosis factor-α production in the MLR compared to PBS injection. Intraperitoneal injection of anti-CD80/86 antibodies significantly prolonged corneal graft survival and decreased IFN-γ+-producing CD4+ T cell frequencies compared to PBS injection. Gene set enrichment analysis showed that the gene sets mainly enriched in the control group were related to allograft rejection and inflammatory response compared to PBS injection. Anti-CD80/86 antibodies significantly prolonged corneal graft survival by inhibiting T-cell proliferation and inflammatory response. |
| first_indexed | 2024-12-13T19:59:43Z |
| format | Article |
| id | doaj.art-9072ac82b6474c48b61ebf85d1f3aeb9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T19:59:43Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9072ac82b6474c48b61ebf85d1f3aeb92022-12-21T23:33:13ZengNature PortfolioScientific Reports2045-23222022-03-0112111210.1038/s41598-022-08949-9Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection modelJun Zhu0Takenori Inomata1Masahiro Nakamura2Keiichi Fujimoto3Yasutsugu Akasaki4Kenta Fujio5Ai Yanagawa6Koichiro Uchida7Jaemyoung Sung8Naoko Negishi9Ken Nagino10Yuichi Okumura11Maria Miura12Hurramhon Shokirova13Mizu Kuwahara14Kunihiko Hirosawa15Akie Midorikawa-Inomata16Atsuko Eguchi17Tianxiang Huang18Hideo Yagita19Sonoko Habu20Ko Okumura21Akira Murakami22Department of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Digital Medicine, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Digital Medicine, Juntendo University Graduate School of MedicineCenter for Immune Therapeutics and Diagnosis, Juntendo UniversityDepartment of Ophthalmology, Juntendo University Graduate School of MedicineAtopy Research Center, Juntendo University Graduate School of MedicineDepartment of Hospital Administration, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Hospital Administration, Juntendo University Graduate School of MedicineDepartment of Hospital Administration, Juntendo University Graduate School of MedicineDepartment of Ophthalmology, Juntendo University Graduate School of MedicineDepartment of Immunology, Juntendo University Graduate School of MedicineAtopy Research Center, Juntendo University Graduate School of MedicineCenter for Immune Therapeutics and Diagnosis, Juntendo UniversityDepartment of Ophthalmology, Juntendo University Graduate School of MedicineAbstract We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-linked immunosorbent assay. Interferon (IFN)-γ-producing CD4+ T cell frequencies in the MLR were assessed using flow cytometry. In vivo, high-risk corneal allograft survival and IFN-γ-producing CD4+ T cell frequencies in corneal grafts were assessed with intraperitoneal injection of anti-CD80/86 antibodies compared to phosphate-buffered saline (PBS). RNA-sequencing was performed on corneal grafts 2 weeks post-transplantation. Anti-CD80/86 antibodies significantly decreased T-cell proliferation, IFN-γ+-producing CD4+ T cell frequencies, and IFN-γ, interleukin (IL)-1β, IL-2, IL-10, and tumor necrosis factor-α production in the MLR compared to PBS injection. Intraperitoneal injection of anti-CD80/86 antibodies significantly prolonged corneal graft survival and decreased IFN-γ+-producing CD4+ T cell frequencies compared to PBS injection. Gene set enrichment analysis showed that the gene sets mainly enriched in the control group were related to allograft rejection and inflammatory response compared to PBS injection. Anti-CD80/86 antibodies significantly prolonged corneal graft survival by inhibiting T-cell proliferation and inflammatory response.https://doi.org/10.1038/s41598-022-08949-9 |
| spellingShingle | Jun Zhu Takenori Inomata Masahiro Nakamura Keiichi Fujimoto Yasutsugu Akasaki Kenta Fujio Ai Yanagawa Koichiro Uchida Jaemyoung Sung Naoko Negishi Ken Nagino Yuichi Okumura Maria Miura Hurramhon Shokirova Mizu Kuwahara Kunihiko Hirosawa Akie Midorikawa-Inomata Atsuko Eguchi Tianxiang Huang Hideo Yagita Sonoko Habu Ko Okumura Akira Murakami Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model Scientific Reports |
| title | Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model |
| title_full | Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model |
| title_fullStr | Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model |
| title_full_unstemmed | Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model |
| title_short | Anti-CD80/86 antibodies inhibit inflammatory reaction and improve graft survival in a high-risk murine corneal transplantation rejection model |
| title_sort | anti cd80 86 antibodies inhibit inflammatory reaction and improve graft survival in a high risk murine corneal transplantation rejection model |
| url | https://doi.org/10.1038/s41598-022-08949-9 |
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