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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| Veröffentlicht in: | International journal of molecular sciences 2021-11, Vol.22 (22), p.12199 |
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| 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. |
| doi_str_mv | 10.3390/ijms222212199 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222212199</identifier><identifier>PMID: 34830080</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Cell activation ; Cell differentiation ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cell proliferation ; Cytokines ; Differentiation ; Ets-1 protein ; Gene expression ; Gene Expression Regulation - immunology ; Genomes ; Homeostasis ; Leukocytes ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Knockout ; Natural killer cells ; Natural Killer T-Cells - immunology ; Promyelocytic Leukemia Zinc Finger Protein - genetics ; Promyelocytic Leukemia Zinc Finger Protein - immunology ; Proto-Oncogene Protein c-ets-1 - genetics ; Proto-Oncogene Protein c-ets-1 - immunology ; Receptors, Antigen, T-Cell, alpha-beta - genetics ; Receptors, Antigen, T-Cell, alpha-beta - immunology ; T cell receptors ; Thymus ; Transcriptomics</subject><ispartof>International journal of molecular sciences, 2021-11, Vol.22 (22), p.12199</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-41995aad5a801b5414de8f6a1e3f81c4b1d41cb0eda925ab0fd9d6b62e5a58043</citedby><cites>FETCH-LOGICAL-c415t-41995aad5a801b5414de8f6a1e3f81c4b1d41cb0eda925ab0fd9d6b62e5a58043</cites><orcidid>0000-0001-6826-9717 ; 0000-0003-0575-914X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34830080$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chuang, Ya-Ting</creatorcontrib><creatorcontrib>Chuang, Wan-Chu</creatorcontrib><creatorcontrib>Liu, Chih-Chun</creatorcontrib><creatorcontrib>Liu, Chia-Wei</creatorcontrib><creatorcontrib>Huang, Yu-Wen</creatorcontrib><creatorcontrib>Yang, Huang-Yu</creatorcontrib><creatorcontrib>Ho, I-Cheng</creatorcontrib><creatorcontrib>Tai, Tzong-Shyuan</creatorcontrib><title>Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><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. 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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. 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| subjects | Animals Cell activation Cell differentiation Cell Differentiation - genetics Cell Differentiation - immunology Cell proliferation Cytokines Differentiation Ets-1 protein Gene expression Gene Expression Regulation - immunology Genomes Homeostasis Leukocytes Lymphocytes Lymphocytes T Mice Mice, Knockout Natural killer cells Natural Killer T-Cells - immunology Promyelocytic Leukemia Zinc Finger Protein - genetics Promyelocytic Leukemia Zinc Finger Protein - immunology Proto-Oncogene Protein c-ets-1 - genetics Proto-Oncogene Protein c-ets-1 - immunology Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - immunology T cell receptors Thymus Transcriptomics |
| title | Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF |
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