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PLZF Acetylation Levels Regulate NKT Cell Differentiation.
Klibi, Jihene; Joseph, Claudine; Delord, Marc; Teissandier, Aurelie; Lucas, Bruno; Chomienne, Christine; Toubert, Antoine; Bourc'his, Deborah; Guidez, Fabien; Benlagha, Kamel.
Afiliación
  • Klibi J; Institut de Recherche Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, INSERM U1160, Paris, France; kamel.benlagha@inserm.fr jihene.klibi@aphp.fr fabien.guidez@inserm.fr.
  • Joseph C; Institut de Recherche Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, INSERM U1160, Paris, France.
  • Delord M; Plateforme de Bioinformatique et Biostatistique, Institut de Recherche Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
  • Teissandier A; Génétique et Biologie du Développement, Institut Curie, CNRS UMR 3215/INSERM U934, Paris, Cedex 05, France.
  • Lucas B; Institut Cochin, Université Paris Descartes, CNRS UMR 8104, INSERM U1016, Paris, France; and.
  • Chomienne C; Institut de Recherche Saint-Louis, Université de Paris, UMRS 1131, INSERM, Paris, France.
  • Toubert A; Institut de Recherche Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, INSERM U1160, Paris, France.
  • Bourc'his D; Génétique et Biologie du Développement, Institut Curie, CNRS UMR 3215/INSERM U934, Paris, Cedex 05, France.
  • Guidez F; Institut de Recherche Saint-Louis, Université de Paris, UMRS 1131, INSERM, Paris, France kamel.benlagha@inserm.fr jihene.klibi@aphp.fr fabien.guidez@inserm.fr.
  • Benlagha K; Institut de Recherche Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, INSERM U1160, Paris, France; kamel.benlagha@inserm.fr jihene.klibi@aphp.fr fabien.guidez@inserm.fr.
J Immunol ; 207(3): 809-823, 2021 08 01.
Article en En | MEDLINE | ID: mdl-34282003
The transcription factor promyelocytic leukemia zinc finger (PLZF) is encoded by the BTB domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional programs. During the development of invariant NKT cells, PLZF is expressed and directs their effector program, but the detailed mechanisms underlying PLZF regulation of multistage NKT cell developmental program are not well understood. This study investigated the role of acetylation-induced PLZF activation on NKT cell development by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON) mice. NKT populations in PLZFON mice were reduced in proportion and numbers of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORγt+ NKT17 subsets dramatically reduced and the emergence of a T-bet-RORγt- NKT cell subset with features of cells in early developmental stages rather than mature NKT2 cells. Preliminary analysis of DNA methylation patterns suggested that activated PLZF acts on the DNA methylation signature to regulate NKT cells' entry into the early stages of development while repressing maturation. In wild-type NKT cells, deacetylation of PLZF is possible, allowing subsequent NKT cell differentiation. Interestingly, development of other innate lymphoid and myeloid cells that are dependent on PLZF for their generation is not altered in PLZFON mice, highlighting lineage-specific regulation. Overall, we propose that specific epigenetic control of PLZF through acetylation levels is required to regulate normal NKT cell differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción de Tipo Kruppel / Células T Asesinas Naturales Límite: Animals Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción de Tipo Kruppel / Células T Asesinas Naturales Límite: Animals Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos