PU.1 expression delineates heterogeneity in primary Th2 cells.
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.
Chang
Hua-Chen
HC
Department of Microbiology and Immunology, and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Zhang
Shangming
S
Thieu
Vivian T
VT
Slee
Roger B
RB
Bruns
Heather A
HA
Laribee
R Nicholas
RN
Klemsz
Michael J
MJ
Kaplan
Mark H
MH
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D012190:Retroviridae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C494748:Gata3 protein, mouse