Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis.

Linlin Niu,Jinzhi Wang,Chaohong Liu,Liling Li,Yukai Jing,Di Yang,Xingtian Xuan,Lisa S Westerberg

doi:10.3389/fimmu.2018.01940

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.

Highlights

Specialty section: This article was submitted toThe invariant NKT(iNKT) cells have a critical role to bridge the innate and adaptive immunity.T Cell Biology, They are generated in thymus and unique αβ T cells characterized by the expression of a semia section of the journal Frontiers in Immunology invariant TCRα and TCRβ chain with limited repertoire (1, 2) that binds to endogenous, microbial, and synthetic lipid ligands presented by CD1d
RT-PCR was applied to confirm the akt[2] gene expression in iNKT and NKT17 cells that are concentrated in stage 2.We found that the akt[2] mRNA levels in iNKT cells were significantly higher than that of CD4+ T cells, which was close to that of
Previous research has shown that NKT cells can be categorized we investigated the cellular mechanism for reduced absolute into NKT1, NKT2, and NKT17 lineages according to PLZF number of Akt[2] KO iNKT cells by evaluating cell proliferation coupled with other signature transcriptional factor staining (6, 7). and apoptosis in vitro

Summary

A United States

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, the role of Akt for development and function of iNKT cells is unknown. 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 Akt[2] KO iNKT cells. Our study has revealed a new intracellular mechanism in which Akt[2] 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

INTRODUCTION

RESULTS

A Akt2 Couples With FoxO-1 to Regulate the Expression of ICOS in NKT Cells

DISCUSSION

24. Erratum