PU.1 Expression Delineates Heterogeneity in Primary Th2 Cells

• DOI: 10.1016/j.immuni.2005.03.016
• Publication Date: 2005-06-22T20:22:47Z
• Authors: Hua-Chen Chang; Shangming Zhang; Vivian T. Thieu; Roger B. Slee; Heather A. Bruns; R. Nicholas Laribee; Michael J. Klemsz; Mark H. Kaplan
• Keywords: 0301 basic medicine; Immunology; Blotting, Western; GATA3 Transcription Factor; Mice; 03 medical and health sciences; Th2 Cells; Proto-Oncogene Proteins; Immunology and Allergy; Animals; Immunoprecipitation; Cells, Cultured; Mice, Inbred BALB C; Reverse Transcriptase Polymerase Chain Reaction; Th1 Cells; Blotting, Northern; Flow Cytometry; DNA-Binding Proteins; Infectious Diseases; Phenotype; Retroviridae; Trans-Activators; Cytokines; Female; RNA Interference

Primary T helper 2 cells are heterogeneous, expressing subsets of cytokines at varying levels. Mechanisms controlling this spectrum of phenotypes are still unclear. The ETS family transcription factor PU.1 is expressed in Th2 but not Th1 cells. Th2 cytokine production is decreased in cultures transduced with a PU.1-expressing retrovirus and increased in Th2 cells following RNAi that decreases PU.1 expression. In primary cultures, PU.1 expression is restricted to a subpopulation of Th2 cells that express CCL22 and a subset of Th2 cytokines. PU.1 regulates the Th2 phenotype by interfering with GATA-3 DNA binding without altering GATA-3 protein levels. Thus, the expression of PU.1 in subsets of Th2 cells establishes a defined cytokine profile and contributes towards establishing the spectrum of cytokine production observed in Th2 populations.