Treg suppression of immunity within inflamed allogeneic grafts
CD4+Foxp3+ regulatory T cells (Tregs) restrain inflammation and immunity. However, the mechanisms underlying Treg suppressor function in inflamed nonlymphoid tissues remain largely unexplored. Here, we restricted immune responses to nonlymphoid tissues and used intravital microscopy to visualize Tre...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-08-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.160579 |
| _version_ | 1827768124615688192 |
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| author | Hehua Dai Andressa Pena Lynne Bauer Amanda Williams Simon C. Watkins Geoffrey Camirand |
| author_facet | Hehua Dai Andressa Pena Lynne Bauer Amanda Williams Simon C. Watkins Geoffrey Camirand |
| author_sort | Hehua Dai |
| collection | DOAJ |
| description | CD4+Foxp3+ regulatory T cells (Tregs) restrain inflammation and immunity. However, the mechanisms underlying Treg suppressor function in inflamed nonlymphoid tissues remain largely unexplored. Here, we restricted immune responses to nonlymphoid tissues and used intravital microscopy to visualize Treg suppression of rejection by effector T cells (Teffs) within inflamed allogeneic islet transplants. Despite their elevated motility, Tregs preferentially contacted antigen-presenting cells (APCs) over Teffs. Interestingly, Tregs specifically targeted APCs that were extensively and simultaneously contacted by Teffs. In turn, Tregs decreased MHC-II expression on APCs and hindered Teff function. Last, we demonstrate that Treg suppressive function within inflamed allografts required ectonucleotidase CD73 activity, which generated the antiinflammatory adenosine. Consequently, CD73–/– Tregs exhibited fewer contacts with APCs within inflamed allografts compared with WT Tregs, but not in spleen. Overall, our findings demonstrate that Tregs suppress immunity within inflamed grafts through CD73 activity and suggest that Treg-APC direct contacts are central to this process. |
| first_indexed | 2024-03-11T12:07:52Z |
| format | Article |
| id | doaj.art-97bb575af0874684bd12e14193f0d03d |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:52Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-97bb575af0874684bd12e14193f0d03d2023-11-07T16:24:28ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-08-01716Treg suppression of immunity within inflamed allogeneic graftsHehua DaiAndressa PenaLynne BauerAmanda WilliamsSimon C. WatkinsGeoffrey CamirandCD4+Foxp3+ regulatory T cells (Tregs) restrain inflammation and immunity. However, the mechanisms underlying Treg suppressor function in inflamed nonlymphoid tissues remain largely unexplored. Here, we restricted immune responses to nonlymphoid tissues and used intravital microscopy to visualize Treg suppression of rejection by effector T cells (Teffs) within inflamed allogeneic islet transplants. Despite their elevated motility, Tregs preferentially contacted antigen-presenting cells (APCs) over Teffs. Interestingly, Tregs specifically targeted APCs that were extensively and simultaneously contacted by Teffs. In turn, Tregs decreased MHC-II expression on APCs and hindered Teff function. Last, we demonstrate that Treg suppressive function within inflamed allografts required ectonucleotidase CD73 activity, which generated the antiinflammatory adenosine. Consequently, CD73–/– Tregs exhibited fewer contacts with APCs within inflamed allografts compared with WT Tregs, but not in spleen. Overall, our findings demonstrate that Tregs suppress immunity within inflamed grafts through CD73 activity and suggest that Treg-APC direct contacts are central to this process.https://doi.org/10.1172/jci.insight.160579ImmunologyTransplantation |
| spellingShingle | Hehua Dai Andressa Pena Lynne Bauer Amanda Williams Simon C. Watkins Geoffrey Camirand Treg suppression of immunity within inflamed allogeneic grafts JCI Insight Immunology Transplantation |
| title | Treg suppression of immunity within inflamed allogeneic grafts |
| title_full | Treg suppression of immunity within inflamed allogeneic grafts |
| title_fullStr | Treg suppression of immunity within inflamed allogeneic grafts |
| title_full_unstemmed | Treg suppression of immunity within inflamed allogeneic grafts |
| title_short | Treg suppression of immunity within inflamed allogeneic grafts |
| title_sort | treg suppression of immunity within inflamed allogeneic grafts |
| topic | Immunology Transplantation |
| url | https://doi.org/10.1172/jci.insight.160579 |
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