Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3

Kittipong Maneechotesuwan, Yao Xin, Kazuhiro Ito, Elen Jazrawi, Kang Yun Lee, Omar S. Usmani, Peter J. Barnes, Ian M. Adcock

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-α. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases.

Original languageEnglish
Pages (from-to)2491-2498
Number of pages8
JournalJournal of Immunology
Volume178
Issue number4
Publication statusPublished - Feb 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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