mTORC2 regulates multiple aspects of NKT-cell development and function

作者：Sklarz Tammarah; Guan Peng; Gohil Mercy; Cotton Renee M; Ge Moyar Q; Haczku Angela; Das Rupali; Jordan Martha S

来源：European Journal of Immunology, 2017, 47(3): 516-526.

DOI：10.1002/eji.201646343

• cytotoxicity
• development
• differentiation
• natural killer Tcell
• signal transduction
• thymus

Invariant NKT (iNKT) cells bridge innate and adaptive immunity by rapidly secreting cytokines and lysing targets following TCR recognition of lipid antigens. Based on their ability to secrete IFN-, IL-4 and IL-17A, iNKT-cells are classified as NKT-1, NKT-2, and NKT-17 subsets, respectively. The molecular pathways regulating iNKT-cell fate are not fully defined. Recent studies implicate Rictor, a required component of mTORC2, in the development of select iNKT-cell subsets, however these reports are conflicting. To resolve these questions, we used Rictor(fl/fl) CD4cre(+) mice and found that Rictor is required for NKT-17 cell development and normal iNKT-cell cytolytic function. Conversely, Rictor is not absolutely required for IL-4 and IFN- production as peripheral iNKT-cells make copious amounts of these cytokines. Overall iNKT-cell numbers are dramatically reduced in the absence of Rictor. We provide data indicating Rictor regulates cell survival as well as proliferation of developing and mature iNKT-cells. Thus, mTORC2 regulates multiple aspects of iNKT-cell development and function.

• 出版日期2017-3