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Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

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Related in: MedlinePlus

LIF is secreted by th2 cells and it negatively regulates IL-4 production.Panel a shows mRNA expression profile of STAT3 upstream molecules. Panel b shows ELISPOT results for IL-4 producing cells in differentially activated populations. Panel c shows results obtained in LIF ELISA experiments. Panel d and e are mRNA expression data adapted form microarray of LIF and IL-6 respectively. Fold change is calculated with respect to untreated sample. In all cases mean of three biological and two technical replicates are shown. Error bars represent standard deviation and * represents significance at p value of less than 0.05 (see text).
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f4: LIF is secreted by th2 cells and it negatively regulates IL-4 production.Panel a shows mRNA expression profile of STAT3 upstream molecules. Panel b shows ELISPOT results for IL-4 producing cells in differentially activated populations. Panel c shows results obtained in LIF ELISA experiments. Panel d and e are mRNA expression data adapted form microarray of LIF and IL-6 respectively. Fold change is calculated with respect to untreated sample. In all cases mean of three biological and two technical replicates are shown. Error bars represent standard deviation and * represents significance at p value of less than 0.05 (see text).

Mentions: Next we sought to investigate which upstream molecules control STAT3 activity during Th2 development. All the known upstream molecules that target STAT3 were searched in the microarray data. We found that LIF was the only molecule that was going up in TCR + IL-4 treated sample as compared to the unstimulated and this upregulation was reversed upon addition of neutralization antibody against IL-4 and IL-4R (Figure 4a). Given the role of LIF as a negative regulator of Th17 differentiation19 and the fact that STAT3 is a known target of LIF and that STAT3 is a positive regulator of Th2 differentiation5, we hypothesized that LIF may positively regulate Th2 differentiation.


Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

LIF is secreted by th2 cells and it negatively regulates IL-4 production.Panel a shows mRNA expression profile of STAT3 upstream molecules. Panel b shows ELISPOT results for IL-4 producing cells in differentially activated populations. Panel c shows results obtained in LIF ELISA experiments. Panel d and e are mRNA expression data adapted form microarray of LIF and IL-6 respectively. Fold change is calculated with respect to untreated sample. In all cases mean of three biological and two technical replicates are shown. Error bars represent standard deviation and * represents significance at p value of less than 0.05 (see text).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376453&req=5

f4: LIF is secreted by th2 cells and it negatively regulates IL-4 production.Panel a shows mRNA expression profile of STAT3 upstream molecules. Panel b shows ELISPOT results for IL-4 producing cells in differentially activated populations. Panel c shows results obtained in LIF ELISA experiments. Panel d and e are mRNA expression data adapted form microarray of LIF and IL-6 respectively. Fold change is calculated with respect to untreated sample. In all cases mean of three biological and two technical replicates are shown. Error bars represent standard deviation and * represents significance at p value of less than 0.05 (see text).
Mentions: Next we sought to investigate which upstream molecules control STAT3 activity during Th2 development. All the known upstream molecules that target STAT3 were searched in the microarray data. We found that LIF was the only molecule that was going up in TCR + IL-4 treated sample as compared to the unstimulated and this upregulation was reversed upon addition of neutralization antibody against IL-4 and IL-4R (Figure 4a). Given the role of LIF as a negative regulator of Th17 differentiation19 and the fact that STAT3 is a known target of LIF and that STAT3 is a positive regulator of Th2 differentiation5, we hypothesized that LIF may positively regulate Th2 differentiation.

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

Show MeSH
Related in: MedlinePlus