Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differenti...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717304631 |
| _version_ | 1818049324021448704 |
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| author | Emeric Limagne Marion Thibaudin Romain Euvrard Hélène Berger Pauline Chalons Frédérique Végan Etienne Humblin Romain Boidot Cédric Rébé Valentin Derangère Sylvain Ladoire Lionel Apetoh Dominique Delmas François Ghiringhelli |
| author_facet | Emeric Limagne Marion Thibaudin Romain Euvrard Hélène Berger Pauline Chalons Frédérique Végan Etienne Humblin Romain Boidot Cédric Rébé Valentin Derangère Sylvain Ladoire Lionel Apetoh Dominique Delmas François Ghiringhelli |
| author_sort | Emeric Limagne |
| collection | DOAJ |
| description | Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription. SIRT1 agonists reduce tumor growth in mice by blocking Th17 cell differentiation. In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels. Altogether, these data underscore that SIRT1 activation impedes Th17 cell differentiation and thereby limits tumor growth and suggest that SIRT1 activators may directly target IL-17A functions. |
| first_indexed | 2024-12-10T10:35:46Z |
| format | Article |
| id | doaj.art-2b9e15673adf411381af1b860df5014f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T10:35:46Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2b9e15673adf411381af1b860df5014f2022-12-22T01:52:26ZengElsevierCell Reports2211-12472017-04-0119474675910.1016/j.celrep.2017.04.004Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 DeacetylationEmeric Limagne0Marion Thibaudin1Romain Euvrard2Hélène Berger3Pauline Chalons4Frédérique Végan5Etienne Humblin6Romain Boidot7Cédric Rébé8Valentin Derangère9Sylvain Ladoire10Lionel Apetoh11Dominique Delmas12François Ghiringhelli13University Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceUniversity Bourgogne Franche-Comté, LNC UMR866, 21000 Dijon, FranceSirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription. SIRT1 agonists reduce tumor growth in mice by blocking Th17 cell differentiation. In cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells and STAT3 acetylation levels. Altogether, these data underscore that SIRT1 activation impedes Th17 cell differentiation and thereby limits tumor growth and suggest that SIRT1 activators may directly target IL-17A functions.http://www.sciencedirect.com/science/article/pii/S2211124717304631SIRT1Th17STAT3RORγtcancer |
| spellingShingle | Emeric Limagne Marion Thibaudin Romain Euvrard Hélène Berger Pauline Chalons Frédérique Végan Etienne Humblin Romain Boidot Cédric Rébé Valentin Derangère Sylvain Ladoire Lionel Apetoh Dominique Delmas François Ghiringhelli Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation Cell Reports SIRT1 Th17 STAT3 RORγt cancer |
| title | Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation |
| title_full | Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation |
| title_fullStr | Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation |
| title_full_unstemmed | Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation |
| title_short | Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via STAT3 Deacetylation |
| title_sort | sirtuin 1 activation controls tumor growth by impeding th17 differentiation via stat3 deacetylation |
| topic | SIRT1 Th17 STAT3 RORγt cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717304631 |
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