TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes
Abstract γδ intestinal intraepithelial lymphocytes (IELs) constitute the majority of IELs with unique CD8αα+ homodimers that are distinct from γδT cells in other tissues. However, it remains largely unclear how those cells develop. Here we show that transforming growth factor beta (TGF-β) signaling...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-023-00542-2 |
| _version_ | 1797811968975831040 |
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| author | Jiajia Han Na Liu Wenwen Jin Peter Zanvit Dunfang Zhang Junji Xu Andrew Bynum Rida Kazmi Jianmin Zhang Wei He WanJun Chen |
| author_facet | Jiajia Han Na Liu Wenwen Jin Peter Zanvit Dunfang Zhang Junji Xu Andrew Bynum Rida Kazmi Jianmin Zhang Wei He WanJun Chen |
| author_sort | Jiajia Han |
| collection | DOAJ |
| description | Abstract γδ intestinal intraepithelial lymphocytes (IELs) constitute the majority of IELs with unique CD8αα+ homodimers that are distinct from γδT cells in other tissues. However, it remains largely unclear how those cells develop. Here we show that transforming growth factor beta (TGF-β) signaling controls the development of TCRγδ+CD8αα+ IELs. Deletion of TGF-β receptors or Smad3 and Smad2 in bone marrow stem cells caused a deficiency of TCRγδ+CD8αα+ IELs in mixed bone marrow chimeric mice. Mechanistically, TGF-β is required for the development of TCRγδ+CD8αα+ IELs thymic precursors (CD44–CD25– γδ thymocytes). In addition, TGF-β signaling induced CD8α in thymic γδT cells and maintained CD8α expression and survival in TCRγδ+CD8αα+ IELs. Moreover, TGF-β also indirectly controls TCRγδ+CD8αα+ IELs by modulating the function of intestinal epithelial cells (IECs). Importantly, TGF-β signaling in TCRγδ+CD8αα+ IELs safeguarded the integrity of the intestinal barrier in dextran sulfate sodium (DSS)-induced colitis. |
| first_indexed | 2024-03-13T07:31:38Z |
| format | Article |
| id | doaj.art-7f896e72d6804bab9a3b9fb5d014b80f |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-03-13T07:31:38Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-7f896e72d6804bab9a3b9fb5d014b80f2023-06-04T11:06:18ZengNature Publishing GroupCell Discovery2056-59682023-05-019111610.1038/s41421-023-00542-2TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytesJiajia Han0Na Liu1Wenwen Jin2Peter Zanvit3Dunfang Zhang4Junji Xu5Andrew Bynum6Rida Kazmi7Jianmin Zhang8Wei He9WanJun Chen10Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthCAMS Key Laboratory for T Cell and Immunotherapy, State Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical CollegeCAMS Key Laboratory for T Cell and Immunotherapy, State Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical CollegeMucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthAbstract γδ intestinal intraepithelial lymphocytes (IELs) constitute the majority of IELs with unique CD8αα+ homodimers that are distinct from γδT cells in other tissues. However, it remains largely unclear how those cells develop. Here we show that transforming growth factor beta (TGF-β) signaling controls the development of TCRγδ+CD8αα+ IELs. Deletion of TGF-β receptors or Smad3 and Smad2 in bone marrow stem cells caused a deficiency of TCRγδ+CD8αα+ IELs in mixed bone marrow chimeric mice. Mechanistically, TGF-β is required for the development of TCRγδ+CD8αα+ IELs thymic precursors (CD44–CD25– γδ thymocytes). In addition, TGF-β signaling induced CD8α in thymic γδT cells and maintained CD8α expression and survival in TCRγδ+CD8αα+ IELs. Moreover, TGF-β also indirectly controls TCRγδ+CD8αα+ IELs by modulating the function of intestinal epithelial cells (IECs). Importantly, TGF-β signaling in TCRγδ+CD8αα+ IELs safeguarded the integrity of the intestinal barrier in dextran sulfate sodium (DSS)-induced colitis.https://doi.org/10.1038/s41421-023-00542-2 |
| spellingShingle | Jiajia Han Na Liu Wenwen Jin Peter Zanvit Dunfang Zhang Junji Xu Andrew Bynum Rida Kazmi Jianmin Zhang Wei He WanJun Chen TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes Cell Discovery |
| title | TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes |
| title_full | TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes |
| title_fullStr | TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes |
| title_full_unstemmed | TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes |
| title_short | TGF-β controls development of TCRγδ+CD8αα+ intestinal intraepithelial lymphocytes |
| title_sort | tgf β controls development of tcrγδ cd8αα intestinal intraepithelial lymphocytes |
| url | https://doi.org/10.1038/s41421-023-00542-2 |
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