Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule
Approximately half of patients with hematologic malignancy who are treated with allogeneic hematopoietic stem cell transplantation (alloHCT) experience graft-versus-host disease (GVHD), which has high mortality rates despite immunosuppressive therapy. IL-12 is known to drive donor T cells toward an...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-06-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI160692 |
| _version_ | 1811329270113370112 |
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| author | James Ferrara Mariano Prado-Acosta |
| author_facet | James Ferrara Mariano Prado-Acosta |
| author_sort | James Ferrara |
| collection | DOAJ |
| description | Approximately half of patients with hematologic malignancy who are treated with allogeneic hematopoietic stem cell transplantation (alloHCT) experience graft-versus-host disease (GVHD), which has high mortality rates despite immunosuppressive therapy. IL-12 is known to drive donor T cells toward an inflammatory Th1 lineage in GVHD, but other mechanisms also promote pathological Th1 alloimmune responses. In this issue of the JCI, Dwyer et al. report on their use of transgenic mice and alloHCT models of GVHD to demonstrate that IL-33 acts directly on donor T cells to increase Tbet expression independently of IL-12. Notably, IL-33 amplified T cell receptor–signaling pathways and inhibited production of regulatory molecules. These findings firmly establish IL-33 as an important costimulatory molecule for Th1 cells during GVHD and provide a target for reducing GVHD, especially in the gastrointestinal (GI) tract, where damage drives mortality. |
| first_indexed | 2024-04-13T15:40:50Z |
| format | Article |
| id | doaj.art-7fa3aa8cdcbb4f68a5d36e31c000a7fb |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-04-13T15:40:50Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-7fa3aa8cdcbb4f68a5d36e31c000a7fb2022-12-22T02:41:08ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-06-0113212Graft-versus-host disease: establishing IL-33 as an important costimulatory moleculeJames FerraraMariano Prado-AcostaApproximately half of patients with hematologic malignancy who are treated with allogeneic hematopoietic stem cell transplantation (alloHCT) experience graft-versus-host disease (GVHD), which has high mortality rates despite immunosuppressive therapy. IL-12 is known to drive donor T cells toward an inflammatory Th1 lineage in GVHD, but other mechanisms also promote pathological Th1 alloimmune responses. In this issue of the JCI, Dwyer et al. report on their use of transgenic mice and alloHCT models of GVHD to demonstrate that IL-33 acts directly on donor T cells to increase Tbet expression independently of IL-12. Notably, IL-33 amplified T cell receptor–signaling pathways and inhibited production of regulatory molecules. These findings firmly establish IL-33 as an important costimulatory molecule for Th1 cells during GVHD and provide a target for reducing GVHD, especially in the gastrointestinal (GI) tract, where damage drives mortality.https://doi.org/10.1172/JCI160692 |
| spellingShingle | James Ferrara Mariano Prado-Acosta Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule The Journal of Clinical Investigation |
| title | Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule |
| title_full | Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule |
| title_fullStr | Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule |
| title_full_unstemmed | Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule |
| title_short | Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule |
| title_sort | graft versus host disease establishing il 33 as an important costimulatory molecule |
| url | https://doi.org/10.1172/JCI160692 |
| work_keys_str_mv | AT jamesferrara graftversushostdiseaseestablishingil33asanimportantcostimulatorymolecule AT marianopradoacosta graftversushostdiseaseestablishingil33asanimportantcostimulatorymolecule |