Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3

Yusuke Endo, Chiaki Iwamura, Makoto Kuwahara, Akane Suzuki, Kaoru Sugaya, Damon J. Tumes, Koji Tokoyoda, Hiroyuki Hosokawa, Masakatsu Yamashita, Toshinori Nakayama

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The regulation of memory CD4 + helper T (Th) cell function, such as polarized cytokine production, remains unclear. Here we show that memory T helper 2 (Th2) cells are divided into four subpopulations by CD62L and CXCR3 expression. All four subpopulations produced interleukin-4 (IL-4) and IL-13, whereas only the CD62L loCXCR3 lo population produced IL-5 accompanied by increased H3-K4 methylation at the Il5 gene locus. The transcription factor Eomesodermin (encoded by Eomes) was highly expressed in memory Th2 cells, whereas its expression was selectively downregulated in the IL-5-producing cells. Il5 expression was enhanced in Eomes-deficient cells, and Eomesodermin was shown to interact with the transcription factor GATA3, preventing GATA3 binding to the Il5 promoter. Memory Th2 cell-dependent airway inflammation was attenuated in the absence of the CD62L loCXCR3 lo population but was enhanced by Eomes-deficient memory Th2 cells. Thus, IL-5 production in memory Th2 cells is regulated by Eomesodermin via the inhibition of GATA3 activity.

Original languageEnglish
Pages (from-to)733-745
Number of pages13
JournalImmunity
Volume35
Issue number5
DOIs
Publication statusPublished - 23 Nov 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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