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Transcription factor p73 regulates Th1 differentiation

Author

Listed:
  • Min Ren

    (National Heart, Lung, and Blood Institute)

  • Majid Kazemian

    (National Heart, Lung, and Blood Institute
    Purdue University)

  • Ming Zheng

    (Stanford University School of Medicine)

  • JianPing He

    (National Institute of Allergy and Infectious Diseases)

  • Peng Li

    (National Heart, Lung, and Blood Institute)

  • Jangsuk Oh

    (National Heart, Lung, and Blood Institute)

  • Wei Liao

    (National Heart, Lung, and Blood Institute)

  • Jessica Li

    (National Heart, Lung, and Blood Institute)

  • Jonathan Rajaseelan

    (National Heart, Lung, and Blood Institute)

  • Brian L. Kelsall

    (National Institute of Allergy and Infectious Diseases)

  • Gary Peltz

    (Stanford University School of Medicine)

  • Warren J. Leonard

    (National Heart, Lung, and Blood Institute)

Abstract

Inter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing to these response differences, here we analyze in vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects Th1 differentiation. In cells differentiated under Th1 conditions in vitro, p73 negatively regulates IFNγ production. p73 binds within, or upstream of, and modulates the expression of Th1 differentiation-related genes such as Ifng and Il12rb2. Furthermore, in mouse experimental autoimmune encephalitis, p73-deficient mice have increased IFNγ production and less disease severity, whereas in an adoptive transfer model of inflammatory bowel disease, transfer of p73-deficient naïve CD4+ T cells increases Th1 responses and augments disease severity. Our results thus identify p73 as a negative regulator of the Th1 immune response, suggesting that p73 dysregulation may contribute to susceptibility to autoimmune disease.

Suggested Citation

  • Min Ren & Majid Kazemian & Ming Zheng & JianPing He & Peng Li & Jangsuk Oh & Wei Liao & Jessica Li & Jonathan Rajaseelan & Brian L. Kelsall & Gary Peltz & Warren J. Leonard, 2020. "Transcription factor p73 regulates Th1 differentiation," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15172-5
    DOI: 10.1038/s41467-020-15172-5
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