title: Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression.
abstract: CD8 T cells play a critical role in protection against viral infections. During effector differentiation, CD8 T cells dramatically change chromatin structure and cellular metabolism, but how energy production increases in response to these epigenetic changes is unknown. We found that loss of basic leucine zipper transcription factor, ATF-like (BATF) inhibited effector CD8 T-cell differentiation. At the late effector stage, BATF was induced by IL-12 and required for IL-12-mediated histone acetylation and survival of effector T cells. BATF, together with c-Jun, transcriptionally inhibited expression of the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase Sirt1, resulting in increased histone acetylation of the T-bet locus and increased cellular NAD(+), which increased ATP production. In turn, high levels of T-bet expression and ATP production promoted effector differentiation and cell survival. These results suggest that BATF promotes effector CD8 T-cell differentiation by regulating both epigenetic remodeling and energy metabolism through Sirt1 expression.
authors.affiliation: Department of Cellular Physiology and Immunology, Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kuroda
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwai
mesh_terms: D000107:Acetylation; D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D056426:Genetic Loci / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009243:NAD / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D006657:Histones; D009243:NAD; D018664:Interleukin-12; D000255:Adenosine Triphosphate; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1