The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes
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- Yasmina Serroukh
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Chunyan Gu-Trantien
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Baharak Hooshiar Kashani
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Matthieu Defrance
- Laboratoire d’Epigénétique du Cancer, Université Libre de Bruxelles, Bruxelles, Belgium
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- Thien-Phong Vu Manh
- Centre d’Immunologie de Marseille-Luminy 13288, Aix Marseille Université UM2, Marseille, France
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- Abdulkader Azouz
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Aurélie Detavernier
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Alice Hoyois
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Jishnu Das
- Ragon Institute of MGH, MIT and Harvard University, Cambridge, United States
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- Martin Bizet
- Laboratoire d’Epigénétique du Cancer, Université Libre de Bruxelles, Bruxelles, Belgium
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- Emeline Pollet
- Centre d’Immunologie de Marseille-Luminy 13288, Aix Marseille Université UM2, Marseille, France
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- Tressy Tabbuso
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Emilie Calonne
- Laboratoire d’Epigénétique du Cancer, Université Libre de Bruxelles, Bruxelles, Belgium
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- Klaas van Gisbergen
- Department of Haematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
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- Marc Dalod
- Centre d’Immunologie de Marseille-Luminy 13288, Aix Marseille Université UM2, Marseille, France
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- François Fuks
- Laboratoire d’Epigénétique du Cancer, Université Libre de Bruxelles, Bruxelles, Belgium
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- Stanislas Goriely
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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- Arnaud Marchant
- Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
書誌事項
- 公開日
- 2018-02-28
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/
- http://creativecommons.org/licenses/by/4.0/
- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.7554/elife.30496
- 公開者
- eLife Sciences Publications, Ltd
説明
<jats:p>Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4CTX-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer.</jats:p>
収録刊行物
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- eLife
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eLife 7 e30496-, 2018-02-28
eLife Sciences Publications, Ltd
