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 Oresic, Harri Lähdesmäki, Omid Rasool, Kanury V. Rao, Tero Aittokallio, Riitta Lahesmaa (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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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
Number of pages11
JournalImmunity
Volume32
Issue number6
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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STAT6 Transcription Factor
Th2 Cells
Interleukin-4
Genome
Cell Differentiation
Immune System Diseases
Helper-Inducer T-Lymphocytes
RNA Interference
Transcriptional Activation
Hypersensitivity
Asthma
T-Lymphocytes
Phenotype
Genes

Cite this

Elo, L. L., Järvenpää, H., Tuomela, S., Raghav, S., Ahlfors, H., Laurila, K., ... 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
Elo, Laura L. ; Järvenpää, Henna ; Tuomela, Soile ; Raghav, Sunil ; Ahlfors, Helena ; Laurila, Kirsti ; Gupta, Bhawna ; Lund, Riikka J. ; Tahvanainen, Johanna ; Hawkins, R. David ; Oresic, Matej ; Lähdesmäki, Harri ; Rasool, Omid ; Rao, Kanury V. ; Aittokallio, Tero ; Lahesmaa, Riitta. / Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming. In: Immunity. 2010 ; Vol. 32, No. 6. pp. 852-862.
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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.",
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Elo, LL, Järvenpää, H, Tuomela, S, Raghav, S, Ahlfors, H, Laurila, K, Gupta, B, Lund, RJ, Tahvanainen, J, Hawkins, RD, Oresic, M, Lähdesmäki, H, Rasool, O, Rao, KV, Aittokallio, T & Lahesmaa, R 2010, 'Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming', Immunity, vol. 32, no. 6, pp. 852-862. https://doi.org/10.1016/j.immuni.2010.06.011

Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming. / Elo, Laura L.; Järvenpää, Henna; Tuomela, Soile; Raghav, Sunil; Ahlfors, Helena; Laurila, Kirsti; Gupta, Bhawna; Lund, Riikka J.; Tahvanainen, Johanna; Hawkins, R. David; Oresic, Matej; Lähdesmäki, Harri; Rasool, Omid; Rao, Kanury V.; Aittokallio, Tero; Lahesmaa, Riitta (Corresponding Author).

In: Immunity, Vol. 32, No. 6, 2010, p. 852-862.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming

AU - Elo, Laura L.

AU - Järvenpää, Henna

AU - Tuomela, Soile

AU - Raghav, Sunil

AU - Ahlfors, Helena

AU - Laurila, Kirsti

AU - Gupta, Bhawna

AU - Lund, Riikka J.

AU - Tahvanainen, Johanna

AU - Hawkins, R. David

AU - Oresic, Matej

AU - Lähdesmäki, Harri

AU - Rasool, Omid

AU - Rao, Kanury V.

AU - Aittokallio, Tero

AU - Lahesmaa, Riitta

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1016/j.immuni.2010.06.011

DO - 10.1016/j.immuni.2010.06.011

M3 - Article

VL - 32

SP - 852

EP - 862

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 6

ER -