title: Bach2 maintains T cells in a naive state by suppressing effector memory-related genes.
abstract: The transcriptional repressor BTB and CNC homology 2 (Bach2) is thought to be mainly expressed in B cells with specific functions such as class switch recombination and somatic hypermutation, but its function in T cells is not known. We found equal Bach2 expression in T cells and analyzed its function using Bach2-deficient (-/-) mice. Although T-cell development was normal, numbers of peripheral naive T cells were decreased, which rapidly produced Th2 cytokines after TCR stimulation. Bach2(-/-) naive T cells highly expressed genes related to effector-memory T cells such as CCR4, ST-2 and Blimp-1. Enhanced expression of these genes induced Bach2(-/-) naive T cells to migrate toward CCR4-ligand and respond to IL33. Forced expression of Bach2 restored the expression of these genes. Using Chromatin Immunoprecipitation (ChIP)-seq analysis, we identified S100 calcium binding protein a, Heme oxigenase 1, and prolyl hydroxylase 3 as Bach2 direct target genes, which are highly expressed in effector-memory T cells. These findings indicate that Bach2 suppresses effector memory-related genes to maintain the naive T-cell state and regulates generation of effector-memory T cells.
authors.affiliation: Laboratory of Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukumo
authors.forename: Midori
authors.initials: M
authors.lastname: Unno
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.forename: Arata
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Kometani
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007156:Immunologic Memory / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013489:Suppression, Genetic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D016207:Cytokines
keywords: CNC family; innate-like lymphocytes; transcription factor