Bach2 maintains T cells in a naive state by suppressing effector memory-related genes

Shin Ichi Tsukumo, Midori Unno, Akihiko Muto, Arata Takeuchi, Kohei Kometani, Tomohiro Kurosaki, Kazuhiko Igarashi, Takashi Saito

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10735-10740
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number26
DOIs
Publication statusPublished - 2013 Jun 25

Keywords

  • CNC family
  • Innate-like lymphocytes
  • Transcription factor

ASJC Scopus subject areas

  • General

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