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 language | English (US) |
|---|---|
| Pages (from-to) | 516-526 |
| Number of pages | 11 |
| Journal | European Journal of Immunology |
| Volume | 47 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2017 |
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Keywords
- cytotoxicity
- development
- differentiation
- natural killer T cell
- signal transduction
- thymus
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
mTORC2 regulates multiple aspects of NKT-cell development and function. / Sklarz, Tammarah; Guan, Peng; Gohil, Mercy; Cotton, Renee M.; Ge, Moyar Q.; Haczku, Angela Franciska; Das, Rupali; Jordan, Martha S.
In: European Journal of Immunology, Vol. 47, No. 3, 01.03.2017, p. 516-526.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - mTORC2 regulates multiple aspects of NKT-cell development and function
AU - Sklarz, Tammarah
AU - Guan, Peng
AU - Gohil, Mercy
AU - Cotton, Renee M.
AU - Ge, Moyar Q.
AU - Haczku, Angela Franciska
AU - Das, Rupali
AU - Jordan, Martha S.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - cytotoxicity
KW - development
KW - differentiation
KW - natural killer T cell
KW - signal transduction
KW - thymus
UR - http://www.scopus.com/inward/record.url?scp=85010952871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85010952871&partnerID=8YFLogxK
U2 - 10.1002/eji.201646343
DO - 10.1002/eji.201646343
M3 - Article
C2 - 28078715
AN - SCOPUS:85010952871
VL - 47
SP - 516
EP - 526
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 3
ER -