Menin controls the memory Th2 cell function by maintaining the epigenetic integrity of Th2 cells

Atsushi Onodera, Masahiro Kiuchi, Kota Kokubo, Miki Kato, Tomohiro Ogino, Shu Horiuchi, Urara Kanai, Kiyoshi Hirahara, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Posttranslational modifications of histones are well-established epigenetic modifications that play an important role in gene expression and regulation. These modifications are partly mediated by the Trithorax group (TrxG) complex, which regulates the induction or maintenance of gene transcription. We investigated the role of Menin, a component of the TrxG complex, in the acquisition and maintenance of Th2 cell identity using T cell-specific Menin-deficient mice. Our gene expression analysis revealed that Menin was involved in the maintenance of the high expression of the previously identified Th2-specific genes rather than the induction of these genes. This result suggests that Menin plays a role in the maintenance of Th2 cell identity. Menin directly bound to the Gata3 gene locus, and this Menin-Gata3 axis appeared to form a core unit of the Th2-specific gene regulatory network. Consistent with the phenotype of Menin-deficient Th2 cells observed in vitro, Menin deficiency resulted in the attenuation of effector Th2 cell-induced airway inflammation. In addition, in memory Th2 (mTh2) cells, Menin was found to play an important role in the maintenance of the expression of Th2-specific genes, including Gata3, Il4, and Il13. Consequently, Menin-deficient mTh2 cells showed an impaired ability to recruit eosinophils to the lung, resulting in the attenuation of mTh2 cell-induced airway inflammation. This study confirmed the critical role of Menin in Th2 cell-mediated immune responses.

Original languageEnglish
Pages (from-to)1153-1162
Number of pages10
JournalJournal of Immunology
Volume199
Issue number3
DOIs
StatePublished - 1 Aug 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Menin controls the memory Th2 cell function by maintaining the epigenetic integrity of Th2 cells'. Together they form a unique fingerprint.

Cite this