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Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation

Author

Listed:
  • Chih-Chung Lin

    (Washington University School of Medicine)

  • Tara R. Bradstreet

    (Washington University School of Medicine)

  • Elizabeth A. Schwarzkopf

    (Washington University School of Medicine)

  • Julia Sim

    (Washington University School of Medicine)

  • Javier A. Carrero

    (Washington University School of Medicine)

  • Chun Chou

    (Washington University School of Medicine)

  • Lindsey E. Cook

    (Washington University School of Medicine)

  • Takeshi Egawa

    (Washington University School of Medicine)

  • Reshma Taneja

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Theresa L. Murphy

    (Washington University School of Medicine)

  • John H. Russell

    (Washington University School of Medicine)

  • Brian T. Edelson

    (Washington University School of Medicine)

Abstract

TH1 and TH17 cells mediate neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Pathogenic TH cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). TH cell pathogenicity in EAE is also regulated by cell-intrinsic production of the immunosuppressive cytokine interleukin 10 (IL-10). Here we demonstrate that mice deficient for the basic helix–loop–helix (bHLH) transcription factor Bhlhe40 (Bhlhe40−/−) are resistant to the induction of EAE. Bhlhe40 is required in vivo in a T cell-intrinsic manner, where it positively regulates the production of GM-CSF and negatively regulates the production of IL-10. In vitro, GM-CSF secretion is selectively abrogated in polarized Bhlhe40−/− TH1 and TH17 cells, and these cells show increased production of IL-10. Blockade of IL-10 receptor in Bhlhe40−/− mice renders them susceptible to EAE. These findings identify Bhlhe40 as a critical regulator of autoreactive T-cell pathogenicity.

Suggested Citation

  • Chih-Chung Lin & Tara R. Bradstreet & Elizabeth A. Schwarzkopf & Julia Sim & Javier A. Carrero & Chun Chou & Lindsey E. Cook & Takeshi Egawa & Reshma Taneja & Theresa L. Murphy & John H. Russell & Bri, 2014. "Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4551
    DOI: 10.1038/ncomms4551
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    Cited by:

    1. BaDoi N. Phan & Madelyn H. Ray & Xiangning Xue & Chen Fu & Robert J. Fenster & Stephen J. Kohut & Jack Bergman & Suzanne N. Haber & Kenneth M. McCullough & Madeline K. Fish & Jill R. Glausier & Qiao S, 2024. "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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