PLZF Acetylation Levels Regulate NKT Cell Differentiation.
Fiche publication
Date publication
août 2021
Journal
Journal of immunology (Baltimore, Md. : 1950)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUIDEZ Fabien
Tous les auteurs :
Klibi J, Joseph C, Delord M, Teissandier A, Lucas B, Chomienne C, Toubert A, Bourc'his D, Guidez F, Benlagha K
Lien Pubmed
Résumé
The transcription factor promyelocytic leukemia zinc finger (PLZF) is encoded by the BTB domain-containing 16 () 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 (PLZF) mice. NKT populations in PLZF 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-betRORγt 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 PLZF 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.
Mots clés
Acetylation, Animals, Cell Differentiation, Immunity, Innate, Kruppel-Like Transcription Factors, genetics, Lymphocytes, metabolism, Mice, Natural Killer T-Cells, metabolism, Promyelocytic Leukemia Zinc Finger Protein
Référence
J Immunol. 2021 08 1;207(3):809-823