Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF
The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12199 |
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| author | Ya-Ting Chuang Wan-Chu Chuang Chih-Chun Liu Chia-Wei Liu Yu-Wen Huang Huang-Yu Yang I-Cheng Ho Tzong-Shyuan Tai |
| author_facet | Ya-Ting Chuang Wan-Chu Chuang Chih-Chun Liu Chia-Wei Liu Yu-Wen Huang Huang-Yu Yang I-Cheng Ho Tzong-Shyuan Tai |
| author_sort | Ya-Ting Chuang |
| collection | DOAJ |
| description | The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells. |
| first_indexed | 2024-03-10T05:26:45Z |
| format | Article |
| id | doaj.art-a20f2071ca934d14be469995d277e9ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:26:45Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a20f2071ca934d14be469995d277e9ba2023-11-22T23:38:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221219910.3390/ijms222212199Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZFYa-Ting Chuang0Wan-Chu Chuang1Chih-Chun Liu2Chia-Wei Liu3Yu-Wen Huang4Huang-Yu Yang5I-Cheng Ho6Tzong-Shyuan Tai7Department of Medical Research, National Taiwan University Hospital, Taipei 10002, TaiwanDepartment of Medical Research, National Taiwan University Hospital, Taipei 10002, TaiwanDepartment of Medical Research, National Taiwan University Hospital, Taipei 10002, TaiwanDepartment of Medical Research, National Taiwan University Hospital, Taipei 10002, TaiwanDepartment of Medical Research, National Taiwan University Hospital, Taipei 10002, TaiwanKidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA 02115, USAAdvanced Immunology Laboratory, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanThe transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells.https://www.mdpi.com/1422-0067/22/22/12199iNKT cellsEts1ICOSPLZF |
| spellingShingle | Ya-Ting Chuang Wan-Chu Chuang Chih-Chun Liu Chia-Wei Liu Yu-Wen Huang Huang-Yu Yang I-Cheng Ho Tzong-Shyuan Tai Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF International Journal of Molecular Sciences iNKT cells Ets1 ICOS PLZF |
| title | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
| title_full | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
| title_fullStr | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
| title_full_unstemmed | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
| title_short | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
| title_sort | ets1 promotes the differentiation of post selected inkt cells through regulation of the expression of vα14jα18 t cell receptor and plzf |
| topic | iNKT cells Ets1 ICOS PLZF |
| url | https://www.mdpi.com/1422-0067/22/22/12199 |
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