title: Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function.
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.
authors.affiliation: Translational Tumor Immunology Group, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Lianjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Translational Tumor Immunology Group, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Benjamin O
authors.initials: BO
authors.lastname: Tschumi
authors.affiliation: Translational Tumor Immunology Group, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Corgnac
authors.affiliation: Biozentrum, University of Basel, 4003 Basel, Switzerland; and.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Rüegg
authors.affiliation: Biozentrum, University of Basel, 4003 Basel, Switzerland; and.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hall
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mach
authors.affiliation: Translational Tumor Immunology Group, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.affiliation: Translational Tumor Immunology Group, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; alena.donda@unil.ch.
authors.forename: Alena
authors.initials: A
authors.lastname: Donda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics*; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099192:CD69 Antigens
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000076223:Regulatory-Associated Protein of mTOR; D058570:TOR Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C540162:Rptor protein, mouse