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Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function

Zhang, Lianjun and Tschumi, Benjamin O. and Corgnac, Stéphanie and Rüegg, Markus A. and Hall, Michael N. and Mach, Jean-Pierre and Romero, Pedro and Donda, Alena. (2014) Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function. Journal of Immunology, 193 (4). pp. 1759-1765.

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Official URL: http://edoc.unibas.ch/dok/A6288991

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Abstract

Invariant NKT (iNKT) cells play critical roles in bridging innate and adaptive immunity. The Raptor containing mTOR complex 1 (mTORC1) has been well documented to control peripheral CD4 or CD8 T cell effector or memory differentiation. However, the role of mTORC1 in iNKT cell development and function remains largely unknown. By using mice with T cell-restricted deletion of Raptor, we show that mTORC1 is selectively required for iNKT but not for conventional T cell development. Indeed, Raptor-deficient iNKT cells are mostly blocked at thymic stage 1-2, resulting in a dramatic decrease of terminal differentiation into stage 3 and severe reduction of peripheral iNKT cells. Moreover, residual iNKT cells in Raptor knockout mice are impaired in their rapid cytokine production upon αGalcer challenge. Bone marrow chimera studies demonstrate that mTORC1 controls iNKT differentiation in a cell-intrinsic manner. Collectively, our data provide the genetic evidence that iNKT cell development and effector functions are under the control of mTORC1 signaling.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association of Immunologists
ISSN:0022-1767
e-ISSN:1550-6606
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2017 14:50
Deposited On:10 Oct 2014 09:19

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