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

Laura L. Elo, Henna Järvenpää, Soile Tuomela, Sunil Raghav, Helena Ahlfors, Kirsti Laurila, Bhawna Gupta, Riikka J. Lund, Johanna Tahvanainen, R. David Hawkins, Matej Orešič, Harri Lähdesmäki, Omid Rasool, Kanury V. Rao, Tero Aittokallio, Riitta Lahesmaa (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)852-862
JournalImmunity
Volume32
Issue number6
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Elo, L. L., Järvenpää, H., Tuomela, S., Raghav, S., Ahlfors, H., Laurila, K., Gupta, B., Lund, R. J., Tahvanainen, J., Hawkins, R. D., Orešič, M., Lähdesmäki, H., Rasool, O., Rao, K. V., Aittokallio, T., & Lahesmaa, R. (2010). Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming. Immunity, 32(6), 852-862. https://doi.org/10.1016/j.immuni.2010.06.011