Stat5 activation plays a critical role in Th2 differentiation.
Upon TCR engagement, naive CD4 T cells differentiate toward the Th1 or Th2 phenotype. IL-4, acting through Stat6, plays a major role in Th2 differentiation; IL-2 has also been reported to be essential. Here, we report that retroviral (RV)-mediated expression of a constitutively active Stat5A mutant (STAT5A1*6) can fully restore IL-4 production when naive CD4 T cells are primed in the absence of IL-2. Furthermore, STAT5A1*6 expression causes Th2 differentiation in the absence of IL-4 or in Stat6- or IL-4Ralpha-deficient cells. Infection with STAT5A1*6-NGFR-RV does not enhance GATA-3 expression. STAT5A1*6-NGFR-RV and GATA-3-GFP-RV each render the Il4 gene accessible, but the sites of restriction enzyme accessibility are different. Stat5A binds to HSII and HSIII sites of the Il4 gene. Coinfection with STAT5A1*6-NGFR-RV and GATA-3-GFP-RV results in optimal Th2 priming.
Zhu
Jinfang
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jfzhu@niaid.nih.gov
Cote-Sierra
Javier
J
Guo
Liying
L
Paul
William E
WE
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins; D019948:Receptors, Interleukin-4 / Q000172:deficiency; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D008894:Milk Proteins; D019948:Receptors, Interleukin-4; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494093:Stat5a protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4