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Lymphocyte Functional Crosstalk and Regulation

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Front. Immunol. | doi: 10.3389/fimmu.2019.01120

ATP triggers human Th9 differentiation via nitric oxide-mediated mTOR-HIF1α pathway

  • 1Translational Health Science and Technology Institute, India

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-tumour 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 creates a feed forward loop in the differentiation of human Th9 cells, as inhibition of purinergic receptor signalling suppressed the generation of human Th9 cells while exogenous NO could rescue generation of Th9 cells even upon inhibition of purinergic receptor signalling. Our findings thus identify that ATP induced nitric oxide potentiate HIF1α-mediated metabolic pathway that leads to IL-9 induction in Th9 cells. Here we identified that the ATP-NO-mTOR-HIF1a 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.

Keywords: T helper cell (Th), Inflammation, T helper 9 cell, Cytokines, Transcription activation

Received: 11 Mar 2019; Accepted: 02 May 2019.

Edited by:

Raghvendra M. Srivastava, Memorial Sloan Kettering Cancer Center, United States

Reviewed by:

Paula M. Oliver, University of Pennsylvania, United States
Manu Rangachari, Laval University, Canada  

Copyright: © 2019 Awasthi and Roy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Amit Awasthi, Translational Health Science and Technology Institute, Gurgaon, India, awasthi005@gmail.com