Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs
Abstract A subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-82945-3 |
| _version_ | 1818754204085256192 |
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| author | Bryan C. Nikolai Prashi Jain David L. Cardenas Brian York Qin Feng Neil J. McKenna Subhamoy Dasgupta David M. Lonard Bert W. O’Malley |
| author_facet | Bryan C. Nikolai Prashi Jain David L. Cardenas Brian York Qin Feng Neil J. McKenna Subhamoy Dasgupta David M. Lonard Bert W. O’Malley |
| author_sort | Bryan C. Nikolai |
| collection | DOAJ |
| description | Abstract A subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs. |
| first_indexed | 2024-12-18T05:19:32Z |
| format | Article |
| id | doaj.art-c5aa049a9d6547ecb096ffd0b12d8bba |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:19:32Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c5aa049a9d6547ecb096ffd0b12d8bba2022-12-21T21:19:42ZengNature PortfolioScientific Reports2045-23222021-02-011111910.1038/s41598-021-82945-3Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human TregsBryan C. Nikolai0Prashi Jain1David L. Cardenas2Brian York3Qin Feng4Neil J. McKenna5Subhamoy Dasgupta6David M. Lonard7Bert W. O’Malley8Department of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineDepartment of Molecular and Cellular Biology, Baylor College of MedicineAbstract A subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.https://doi.org/10.1038/s41598-021-82945-3 |
| spellingShingle | Bryan C. Nikolai Prashi Jain David L. Cardenas Brian York Qin Feng Neil J. McKenna Subhamoy Dasgupta David M. Lonard Bert W. O’Malley Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs Scientific Reports |
| title | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs |
| title_full | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs |
| title_fullStr | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs |
| title_full_unstemmed | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs |
| title_short | Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs |
| title_sort | steroid receptor coactivator 3 src 3 aib1 is enriched and functional in mouse and human tregs |
| url | https://doi.org/10.1038/s41598-021-82945-3 |
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