Bilirubin Promotes De Novo Generation of T Regulatory Cells
We have previously demonstrated that bilirubin administration to the recipient induces tolerance towards islet cell transplants across a complete MHC mismatch in a mouse model. Here we assess the mechanisms of such protection. Bilirubin treatment of recipients improved function of islet allografts b...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2010-04-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368909X484680 |
| _version_ | 1811289387485364224 |
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| author | Fredy Rocuts Xinyu Zhang Jun Yan Yinan Yue Michael Thomas Fritz H. Bach Eva Czismadia Hongjun Wang Ph.D. |
| author_facet | Fredy Rocuts Xinyu Zhang Jun Yan Yinan Yue Michael Thomas Fritz H. Bach Eva Czismadia Hongjun Wang Ph.D. |
| author_sort | Fredy Rocuts |
| collection | DOAJ |
| description | We have previously demonstrated that bilirubin administration to the recipient induces tolerance towards islet cell transplants across a complete MHC mismatch in a mouse model. Here we assess the mechanisms of such protection. Bilirubin treatment of recipients improved function of islet allografts by suppressing expressions of proinflammatory and proapoptotic genes in those islets and by increasing Foxp3 + T regulatory (Treg) cells at the site of transplanted islets at various days after transplantation. No prolongation of graft survival was observed in recipients treated with bilirubin when CD4 + CD25 + T cells were predepleted from those recipients, indicating that Treg cells are necessary for the protective effect of bilirubin. Adoptive transfer of Treg cells from tolerant mice into Rag1 -/- recipients resulted in long-term acceptance of skin allografts in an alloantigen-specific manner, suggesting that Treg cells are sufficient to induce tolerance. In addition, bilirubin treatment promoted de novo generation of Treg cells in Rag1 -/- recipients. Thus, bilirubin treatment to the recipients prolongs islet allograft survival via a Treg-dependent manner in which CD4 + CD25 + Treg cells are both necessary and sufficient for tolerance induction and graft acceptance. Bilirubin treatment promotes de novo generation of Treg cells that might account for the protective effects of bilirubin given to recipients. |
| first_indexed | 2024-04-13T03:54:16Z |
| format | Article |
| id | doaj.art-03c5f16a4d3944828cb9c01d20548372 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-04-13T03:54:16Z |
| publishDate | 2010-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-03c5f16a4d3944828cb9c01d205483722022-12-22T03:03:42ZengSAGE PublishingCell Transplantation0963-68971555-38922010-04-011910.3727/096368909X484680Bilirubin Promotes De Novo Generation of T Regulatory CellsFredy Rocuts0Xinyu Zhang1Jun Yan2Yinan Yue3Michael Thomas4Fritz H. Bach5Eva Czismadia6Hongjun Wang Ph.D.7 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAWe have previously demonstrated that bilirubin administration to the recipient induces tolerance towards islet cell transplants across a complete MHC mismatch in a mouse model. Here we assess the mechanisms of such protection. Bilirubin treatment of recipients improved function of islet allografts by suppressing expressions of proinflammatory and proapoptotic genes in those islets and by increasing Foxp3 + T regulatory (Treg) cells at the site of transplanted islets at various days after transplantation. No prolongation of graft survival was observed in recipients treated with bilirubin when CD4 + CD25 + T cells were predepleted from those recipients, indicating that Treg cells are necessary for the protective effect of bilirubin. Adoptive transfer of Treg cells from tolerant mice into Rag1 -/- recipients resulted in long-term acceptance of skin allografts in an alloantigen-specific manner, suggesting that Treg cells are sufficient to induce tolerance. In addition, bilirubin treatment promoted de novo generation of Treg cells in Rag1 -/- recipients. Thus, bilirubin treatment to the recipients prolongs islet allograft survival via a Treg-dependent manner in which CD4 + CD25 + Treg cells are both necessary and sufficient for tolerance induction and graft acceptance. Bilirubin treatment promotes de novo generation of Treg cells that might account for the protective effects of bilirubin given to recipients.https://doi.org/10.3727/096368909X484680 |
| spellingShingle | Fredy Rocuts Xinyu Zhang Jun Yan Yinan Yue Michael Thomas Fritz H. Bach Eva Czismadia Hongjun Wang Ph.D. Bilirubin Promotes De Novo Generation of T Regulatory Cells Cell Transplantation |
| title | Bilirubin Promotes De Novo Generation of T Regulatory Cells |
| title_full | Bilirubin Promotes De Novo Generation of T Regulatory Cells |
| title_fullStr | Bilirubin Promotes De Novo Generation of T Regulatory Cells |
| title_full_unstemmed | Bilirubin Promotes De Novo Generation of T Regulatory Cells |
| title_short | Bilirubin Promotes De Novo Generation of T Regulatory Cells |
| title_sort | bilirubin promotes de novo generation of t regulatory cells |
| url | https://doi.org/10.3727/096368909X484680 |
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