Interaction between GATA-3 and the transcriptional coregulator Pias1 is important for the regulation of Th2 immune responses

J Immunol. 2007 Dec 15;179(12):8297-304. doi: 10.4049/jimmunol.179.12.8297.


Th2 cytokine expression is dependent on the transcription factor GATA-3. However, the molecular interactions of GATA-3 leading to Th2 cytokine gene activation have not been well characterized. Here, we reported a number of GATA-3 associated proteins in Th2 cells, and one of such proteins Pias1 functioned as a positive transcriptional coregulator for GATA-3. When overexpressed in Th2 cells, Pias1 enhanced the expression of IL-13, and to lesser degrees, IL-4 and -5. Conversely, Pias1 siRNA down-regulated the Th2 cytokine expression. In Leishmania major infection, manipulating Pias1 expression in parasite-reactive CD4 T cells altered severity of disease caused by Th2 responses. Mechanistically, Pias1 markedly potentiated GATA-3-mediated activation of the IL-13 promoter by facilitating the recruitment of GATA-3 to the promoter. In contrast, IL-5 promoter was modestly enhanced by Pias1 and no effect was observed on IL-4 promoter. Thus, both promoter activation and additional mechanisms are responsible for regulation by Pias1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • GATA3 Transcription Factor / metabolism*
  • Humans
  • Immunity / genetics*
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Leishmania major
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology
  • Mice
  • Promoter Regions, Genetic
  • Protein Inhibitors of Activated STAT / antagonists & inhibitors
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • RNA, Small Interfering / genetics
  • Retroviridae / genetics
  • Th2 Cells / immunology*
  • Transcription, Genetic
  • Two-Hybrid System Techniques


  • Cytokines
  • GATA3 Transcription Factor
  • Interleukin-13
  • Interleukin-5
  • Pias1 protein, mouse
  • Protein Inhibitors of Activated STAT
  • RNA, Small Interfering
  • Interleukin-4