Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis
As a critical linker between mTORC1 and mTORC2, Akt is important for the cell metabolism. The role of Akt in the function and development of B and T cells is well characterized, however, the role of Akt for development and function of iNKT cells is unknown. iNKT cells bridge the adaptive and innate...
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| Format: | Article |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01940/full |
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| author | LinLin Niu LinLin Niu LinLin Niu Xingtian Xuan Xingtian Xuan Xingtian Xuan Jinzhi Wang Jinzhi Wang Jinzhi Wang Liling Li Liling Li Liling Li Di Yang Di Yang Di Yang Yukai Jing Lisa S. Westerberg Chaohong Liu |
| author_facet | LinLin Niu LinLin Niu LinLin Niu Xingtian Xuan Xingtian Xuan Xingtian Xuan Jinzhi Wang Jinzhi Wang Jinzhi Wang Liling Li Liling Li Liling Li Di Yang Di Yang Di Yang Yukai Jing Lisa S. Westerberg Chaohong Liu |
| author_sort | LinLin Niu |
| collection | DOAJ |
| description | As a critical linker between mTORC1 and mTORC2, Akt is important for the cell metabolism. The role of Akt in the function and development of B and T cells is well characterized, however, the role of Akt for development and function of iNKT cells is unknown. iNKT cells bridge the adaptive and innate immunity, and in this study, we found that the differentiation of NKT17 cells and IL17 production of NKT17 cells were disrupted in Akt2 KO mice. ICOS has been demonstrated to be critical for the differentiation of NKT17 cells and we found that ICOS mRNA and protein expression was reduced in Akt2 KO iNKT cells. As a consequence, phosphorylation of FoxO-1 was downregulated in Akt2 KO thymocytes but the sequestration of FoxO-1 in the nucleus of Akt2 KO iNKT cells was increased. The negative feedback loop between ICOS and FoxO-1 has been demonstrated in CD4+T follicular helper cells. Therefore our study has revealed a new intracellular mechanism in which Akt2 regulates ICOS expression via FoxO-1 and this signaling axis regulates the differentiation and function of NKT17 cells. This study provides a new linker between cell metabolism and function of iNKT cells. |
| first_indexed | 2024-12-11T01:38:25Z |
| format | Article |
| id | doaj.art-fdf27aa202fb4fb28e8f35dcc8ac0d88 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T01:38:25Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fdf27aa202fb4fb28e8f35dcc8ac0d882022-12-22T01:25:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.01940349569Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS AxisLinLin Niu0LinLin Niu1LinLin Niu2Xingtian Xuan3Xingtian Xuan4Xingtian Xuan5Jinzhi Wang6Jinzhi Wang7Jinzhi Wang8Liling Li9Liling Li10Liling Li11Di Yang12Di Yang13Di Yang14Yukai Jing15Lisa S. Westerberg16Chaohong Liu17Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Chongqing, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Chongqing, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Chongqing, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Chongqing, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, ChinaAs a critical linker between mTORC1 and mTORC2, Akt is important for the cell metabolism. The role of Akt in the function and development of B and T cells is well characterized, however, the role of Akt for development and function of iNKT cells is unknown. iNKT cells bridge the adaptive and innate immunity, and in this study, we found that the differentiation of NKT17 cells and IL17 production of NKT17 cells were disrupted in Akt2 KO mice. ICOS has been demonstrated to be critical for the differentiation of NKT17 cells and we found that ICOS mRNA and protein expression was reduced in Akt2 KO iNKT cells. As a consequence, phosphorylation of FoxO-1 was downregulated in Akt2 KO thymocytes but the sequestration of FoxO-1 in the nucleus of Akt2 KO iNKT cells was increased. The negative feedback loop between ICOS and FoxO-1 has been demonstrated in CD4+T follicular helper cells. Therefore our study has revealed a new intracellular mechanism in which Akt2 regulates ICOS expression via FoxO-1 and this signaling axis regulates the differentiation and function of NKT17 cells. This study provides a new linker between cell metabolism and function of iNKT cells.https://www.frontiersin.org/article/10.3389/fimmu.2018.01940/fullAkt2iNKTICOSNKT17FoxO-1 |
| spellingShingle | LinLin Niu LinLin Niu LinLin Niu Xingtian Xuan Xingtian Xuan Xingtian Xuan Jinzhi Wang Jinzhi Wang Jinzhi Wang Liling Li Liling Li Liling Li Di Yang Di Yang Di Yang Yukai Jing Lisa S. Westerberg Chaohong Liu Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis Frontiers in Immunology Akt2 iNKT ICOS NKT17 FoxO-1 |
| title | Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis |
| title_full | Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis |
| title_fullStr | Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis |
| title_full_unstemmed | Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis |
| title_short | Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis |
| title_sort | akt2 regulates the differentiation and function of nkt17 cells via foxo 1 icos axis |
| topic | Akt2 iNKT ICOS NKT17 FoxO-1 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01940/full |
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