Dataset Information

ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1? Pathway.

ABSTRACT: Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial effector function in inducing allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. Although the cytokines that lead to the differentiation of human Th9 cells have been identified, other factors that support the differentiation of Th9 cells have not been identified yet. Here we show that the extracellular ATP (eATP) induces the differentiation of Th9 cells. We further show that eATP induces the production of nitric oxide (NO), which create a feed forward loop in the differentiation of human Th9 cells, as inhibition of purinergic receptor signaling suppressed the generation of human Th9 cells while exogenous NO could rescue generation of Th9 cells even upon inhibition of purinergic receptor signaling. Moreover, we show that ATP promotes mTOR and HIF1? dependent generation of Th9 cells. Our findings thus identify that ATP induced nitric oxide potentiate HIF1?-mediated metabolic pathway that leads to IL-9 induction in Th9 cells. Here we identified that the ATP-NO-mTOR-HIF1? axis is essential for the generation of human Th9 cells and modulation of this axis may lead to therapeutic intervention of Th9-associated disease conditions.

SUBMITTER: Roy S

PROVIDER: S-EPMC6536008 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1α Pathway.

Roy Suyasha S Awasthi Amit A

Frontiers in immunology 20190520

Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial effector function in inducing allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. Although the cytokines that lead to the differentiation of human Th9 cells have been identified, other factors that support the differentiation of Th9 cells have not been identified yet. Here we show that the extracellular ATP (eATP) induces the differentiation of Th9 cells. We further show that ...[more]

PMID: 31164892

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Project description:Of all the essential nutrients, nitrogen is the one most often limiting for plant growth. Nitrogen can be taken up by plants in two ways. One possibility is through ammonium and nitrate, which are the predominate inorganic forms of nitrogen in soils. The second possibility is the uptake of air-born nitrogen through plant-associated mircoorganisms in root nodules. The majority of plants able to form such nitrogen-fixing root nodules are in the legume family Fabaceae. Here we present a third possibility M-bM-^@M-^S a new pathway, termed as nitric oxide (NO)-fixation pathway, which allows plants to fix atmospheric NO and to use it for better growth and development. We identified non-symbiotic hemoglobin class 1 (AtGLB1) and class 2 (AtGLB2) as key proteins of the NO-fixation pathway. In an NO enriched environment NO-fixation is enhanced considerably in plants overexpressing AtGLB1 or AtGLB2 genes. NO uptake resulted in four-fold higher nitrate levels in these plants compared to NO-treated wild-type plants. Correspondingly, the growth parameters like rosettes size and weight, vegetative shoot thickness and also seed yield were 25%, 40%, 30%, and 20% higher, respectively, in the overexpression lines in comparison to wild-type plants. Our results highlight the existence of a NO-fixing pathway in plants. We demonstrated that plant non-symbiotic hemoglobin proteins can fix atmospheric NO and convert it to nitrate, which is further introduced into the N-metabolism. We assume that our results might provide new insights into the field of crop science research and that the NO-fixation capability might serve as a new economically important breeding trait for enhancing biomass, fruit, and seed production. Modifying this pathway might be a promising approach for better and more environment-friendly supply of nitrogen. For example crop plant hemoglobin proteins could be improved for their NO-fixing capability and their expression levels could be increased. WT-Arabidopsis thaliana plants were fumigated with Ambient NO and 3 ppm NO air in three completely independent biological experiments. Total RNA was isolated from four-week old rosette leaves of these plants to determine the gene expression signature of each samples using Agilent one-color microarray. Differences in the gene expression signatures between Ambient NO and 3 ppm NO treated samples were analyzed to see the effect of NO fumigation on the WT Arabidopsis plants at the transcript level.

Dataset Information

ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1? Pathway.

Publications

ATP Triggers Human Th9 Cell Differentiation via Nitric Oxide-Mediated mTOR-HIF1α Pathway.

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