Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.

Biomathematics Research Group, Department of Mathematics, University of Turku, FI-20014 Turku, Finland.
Immunity (Impact Factor: 19.75). 06/2010; 32(6):852-62. DOI: 10.1016/j.immuni.2010.06.011
Source: PubMed

ABSTRACT Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.

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