mTORC2 regulates multiple aspects of NKT-cell development and function

Tammarah Sklarz, Peng Guan, Mercy Gohil, Renee M. Cotton, Moyar Q. Ge, Angela Franciska Haczku, Rupali Das, Martha S. Jordan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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-γ, 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 Rictorfl/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-γ 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.

Original languageEnglish (US)
Pages (from-to)516-526
Number of pages11
JournalEuropean Journal of Immunology
Volume47
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • cytotoxicity
  • development
  • differentiation
  • natural killer T cell
  • signal transduction
  • thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sklarz, T., Guan, P., Gohil, M., Cotton, R. M., Ge, M. Q., Haczku, A. F., Das, R., & Jordan, M. S. (2017). mTORC2 regulates multiple aspects of NKT-cell development and function. European Journal of Immunology, 47(3), 516-526. https://doi.org/10.1002/eji.201646343