title: SLAM-associated protein favors the development of iNKT2 over iNKT17 cells.
abstract: 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.
authors.affiliation: Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR 1151, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Michel
authors.affiliation: Laboratory of Lymphocyte Activation and EBV Susceptibility, INSERM UMR 1163, Institut des Maladies Génétiques, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lenoir
authors.affiliation: Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR 1151, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Massot
authors.affiliation: Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR 1151, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Diem
authors.affiliation: Laboratory of Lymphocyte Activation and EBV Susceptibility, INSERM UMR 1163, Institut des Maladies Génétiques, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Pasquier
authors.affiliation: Lymphoid Tissue Development Unit, Institut Pasteur, Paris, France.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sawa
authors.affiliation: Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR 1151, Paris, France.|Institut Imagine, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rignault-Bricard
authors.affiliation: Hôpital Cochin-St. Vincent de Paul, INSERM UMR 986, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
authors.affiliation: Lymphoid Tissue Development Unit, Institut Pasteur, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Québec, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Veillette
authors.affiliation: Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR 1151, Paris, France.|Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Leite-de-Moraes
authors.affiliation: Laboratory of Lymphocyte Activation and EBV Susceptibility, INSERM UMR 1163, Institut des Maladies Génétiques, Hôpital Necker-Enfants Malades, Paris, France. sylvain.latour@inserm.fr.|Institut Imagine, Université Paris Descartes Sorbonne Paris Cité, Paris, France. sylvain.latour@inserm.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010641:Phenotype; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D015847:Interleukin-4
keywords: IL-17; IL-4; PLZF; SAP; Thymic development; iNKT cells