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. PUA regulates the Th2 phenotype by interfering with GATA-3 DNA binding without altering GATA-3 protein levels. Thus, the expression of PUA in subsets of Th2 cells establishes a defined cytokine profile and contributes towards establishing the spectrum of cytokine production observed in Th2 populations.