SLAM-associated protein favors the development of iNKT2 over iNKT17 cells

Autor: Maria Leite-de-Moraes, Sylvain Latour, Gérard Eberl, Séverine Diem, Rachel Rignault-Bricard, Benoit Pasquier, Agnès Lehuen, André Veillette, Marie Laure Michel, Shinichiro Sawa, Bérangère Massot, Christelle Lenoir
Přispěvatelé: Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Coordination des Cellules et Morphogenèse / Heart Morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, This work was supported by grants from INSERM (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre National de la Recherche Scientifique), ANR (Agence Nationale de la Recherche, ANR‐08‐MIEN‐012‐01, ANR‐2010‐MIDI‐005, and ANR‐10‐IAHU‐01), the Fondation ARC pour la Recherche sur le Cancer (France), the European Research Council (ERC‐2009‐AdG_20090506 n°FP7‐249816), and the Rare Diseases Fondation (France)., ANR-08-MIEN-0012,GENEBV,Susceptibilité génétique à l'infection par l'EBV et lymphocytes NKT(2008), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 249816,EC:FP7:ERC,ERC-2009-AdG,PIDIMMUN(2010), Université Paris Descartes - Paris 5 (UPD5)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2016
Předmět:
0301 basic medicine
MESH: Nuclear Receptor Subfamily 1
Group F
Member 3
Cellular differentiation
medicine.medical_treatment
MESH: Interleukin-17
[SDV]Life Sciences [q-bio]
PLZF
Retinoic acid
MESH: T-Lymphocyte Subsets
Thymic development
MESH: Mice
Knockout
chemistry.chemical_compound
Mice
0302 clinical medicine
T-Lymphocyte Subsets
Immunology and Allergy
MESH: Animals
Signaling Lymphocytic Activation Molecule Associated Protein
Cells
Cultured
Orphan receptor
Mice
Knockout
Interleukin-17
Cell Differentiation
Nuclear Receptor Subfamily 1
Group F
Member 3
Natural killer T cell
Cell biology
IL-17
Cytokine
Phenotype
SAP
MESH: Cells
Cultured
MESH: Cell Differentiation
MESH: Immunophenotyping
MESH: Mice
Transgenic
Immunology
Mice
Transgenic
MESH: Signaling Lymphocytic Activation Molecule Associated Protein
Cell fate determination
Biology
MESH: Phenotype
Immunophenotyping
03 medical and health sciences
medicine
Animals
Transcription factor
MESH: Mice
Interleukin 4
iNKT cells
IL-4
MESH: Interleukin-4
030104 developmental biology
chemistry
MESH: Natural Killer T-Cells
MESH: Biomarkers
Natural Killer T-Cells
Interleukin-4
Biomarkers
030215 immunology
Zdroj: European Journal of Immunology
European Journal of Immunology, 2016, 46 (9), pp.2162-2174. ⟨10.1002/eji.201646313⟩
European Journal of Immunology, Wiley-VCH Verlag, 2016, 46 (9), pp.2162-2174. ⟨10.1002/eji.201646313⟩
ISSN: 1521-4141
0014-2980
Popis: International audience; Invariant NKT (iNKT) cells differentiate in the thymus into three distinct lineages defined by their cytokine and transcription factor expression. Signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) is essential for early stages of iNKT cell development, but its role during terminal differentiation of iNKT1, iNKT2, or iNKT17 cells remains unclear. Taking advantage of SAP-deficient mice expressing a Vα14-Jα18 TCRα transgene, we found that SAP is critical not only for IL-4 production but also for the terminal differentiation of IL-4-producing iNKT2 cells. Furthermore, without SAP, the IL-17 producing subset is expanded, while IFN-γ-producing iNKT1 differentiation is only moderately compromised. Lack of SAP reduced the expression of the transcription factors GATA-3 and promyelocytic leukemia zinc finger, but enhanced the levels of retinoic acid receptor-related orphan receptor γt. In the absence of SAP, lineage commitment was actually shifted toward the emergence of iNKT17 over iNKT2 cells. Collectively, our data unveil a new critical regulatory function for SAP in thymic iNKT cell fate decisions.
Databáze: OpenAIRE
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