Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis
Authors: Lisa S Westerberg
Yukai Jing
Xingtian Xuan
Chaohong Liu
Jinzhi Wang
LinLin Niu
Liling Li
Di Yang
Journal: Frontiers in Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: Akt2; FoxO-1; ICOS; NKT17; iNKT.
Affiliations: Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China., Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China., Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China., Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China., Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 3J: two flow cytometry panels look more similar to each other than expected. Although the gated percentages are different and certain areas of the plots look different, the areas I marked below in yellow and red look very similar. ![file] , 
 September 2020 correction: https: www.frontiersin.org articles 10.3389 fimmu.2020.589346 full It reads:  *In the original article, there was a mistake in Figure 3J and Figure 4R as published. We used the wrong flow plot of KO thymus in the upper panel of Figure 3J and Figure 4R due to an accidental error. The corrected Figure 3 and Figure 4 appear below. * , 
 #2 Please note, the correction only mentions the KO figure in 3J is wrong but WT is correct. However, in the correction, both WT and KO have been replaced quietly. In addition, other parameters and values on those two figures are exact the same. , 
 March 31 2021 retraction: https: www.frontiersin.org articles 10.3389 fimmu.2021.686304 full It reads:  The journal and Chief Editors retract the 12 September 2018 article cited above. Following the publication of the article, image duplication concerns were identified in the published article, specifically in Figure 3J. The authors were unable to provide a satisfactory explanation for this occurrence despite issuing a Correction article. As a result, the data and conclusions of the article have been deemed unreliable. The article is therefore being retracted. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors and readers of Frontiers in Immunology. I thank the journal for their action. ,