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Transcription factor Foxo1 is essential for IL-9 induction in T helper cells

Author

Listed:
  • Sakshi Malik

    (Translational Health Science & Technology Institute)

  • Srikanth Sadhu

    (Translational Health Science & Technology Institute)

  • Srikanth Elesela

    (Translational Health Science & Technology Institute)

  • Ramendra Pati Pandey

    (Translational Health Science & Technology Institute)

  • Amanpreet Singh Chawla

    (National Institute of Immunology)

  • Deepak Sharma

    (Indian Institute of Technology Roorkee)

  • Lipsa Panda

    (Institute of Genomics and Integrative Biology (IGIB))

  • Deepak Rathore

    (Translational Health Science & Technology Institute)

  • Balram Ghosh

    (Institute of Genomics and Integrative Biology (IGIB))

  • Vineet Ahuja

    (All India Institute of Medical Sciences (AIIMS))

  • Amit Awasthi

    (Translational Health Science & Technology Institute)

Abstract

Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3+ regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTreg cells. Furthermore, loss of Foxo1 attenuates IL-9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells.

Suggested Citation

  • Sakshi Malik & Srikanth Sadhu & Srikanth Elesela & Ramendra Pati Pandey & Amanpreet Singh Chawla & Deepak Sharma & Lipsa Panda & Deepak Rathore & Balram Ghosh & Vineet Ahuja & Amit Awasthi, 2017. "Transcription factor Foxo1 is essential for IL-9 induction in T helper cells," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00674-6
    DOI: 10.1038/s41467-017-00674-6
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    Cited by:

    1. Srikanth Sadhu & Rajdeep Dalal & Jyotsna Dandotiya & Akshay Binayke & Virendra Singh & Manas Ranjan Tripathy & Vinayaka Das & Sandeep Goswami & Shakti Kumar & Zaigham Abbas Rizvi & Amit Awasthi, 2023. "IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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