Kittipong ManeechotesuwanYao XinKazuhiro ItoElen JazrawiKang Yun LeeOmar S. UsmaniPeter J. BarnesIan M. AdcockNational Heart and Lung InstituteMahidol University2018-08-242018-08-242007-02-15Journal of Immunology. Vol.178, No.4 (2007), 2491-2498002217672-s2.0-33846935457https://repository.li.mahidol.ac.th/handle/20.500.14594/24578GATA-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. Copyright © 2007 by The American Association of Immunologists, Inc.Mahidol UniversityImmunology and MicrobiologyArticleSCOPUS10.4049/jimmunol.178.4.2491