Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity

PLoS One. 2013 Jun 18;8(6):e66468. doi: 10.1371/journal.pone.0066468. Print 2013.

Abstract

Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Profiling*
  • Gene Knockdown Techniques
  • Immunologic Memory
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / genetics
  • Receptors, Cytokine / genetics
  • Th2 Cells / cytology*
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • RNA, Small Interfering
  • Receptors, Cytokine

Grant support

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Genome Science” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No.221S0002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.