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IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1

Author

Listed:
  • Christina Heinemann

    (Klinikum rechts der Isar, Technische Universität München)

  • Sylvia Heink

    (Klinikum rechts der Isar, Technische Universität München)

  • Franziska Petermann

    (Klinikum rechts der Isar, Technische Universität München)

  • Ajithkumar Vasanthakumar

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Veit Rothhammer

    (Klinikum rechts der Isar, Technische Universität München)

  • Elien Doorduijn

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Meike Mitsdoerffer

    (Klinikum rechts der Isar, Technische Universität München)

  • Christopher Sie

    (Klinikum rechts der Isar, Technische Universität München)

  • Olivia Prazeres da Costa

    (Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München)

  • Thorsten Buch

    (Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München)

  • Bernhard Hemmer

    (Klinikum rechts der Isar, Technische Universität München
    Munich Cluster for Systems Neurology (SyNergy))

  • Mohamed Oukka

    (Seattle Children’s Hospital, Center for Immunity and Immunotherapies, University of Washington School of Medicine)

  • Axel Kallies

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Thomas Korn

    (Klinikum rechts der Isar, Technische Universität München
    Munich Cluster for Systems Neurology (SyNergy))

Abstract

Central nervous system (CNS) autoimmunity is regulated by the balance of pro-inflammatory cytokines and IL-10. Here we identify the transcriptional regulator Blimp1 as crucial to induce IL-10 in inflammatory T helper cells. Pre-committed Th17 cells respond to IL-27 and IL-12 by upregulating Blimp1 and adopt a Tr-1-like phenotype characterized by IL-10 and IFN-γ production. Accordingly, Blimp1-deficient effector T cells fail to produce IL-10, and deficiency in Tr-1 cell function leads to uncontrolled Th17 cell-driven CNS pathology without the need to stabilize the Th17 phenotype with IL-23. IL-23 counteracts IL-27 and IL-12-mediated effects on Tr-1-development reinforcing the pro-inflammatory phenotype of Th17 cells. Thus, the balance of IL-23 vs IL-12/IL-27 signals into CD4+ effector T cells determines whether tissue inflammation is perpetuated or resolves.

Suggested Citation

  • Christina Heinemann & Sylvia Heink & Franziska Petermann & Ajithkumar Vasanthakumar & Veit Rothhammer & Elien Doorduijn & Meike Mitsdoerffer & Christopher Sie & Olivia Prazeres da Costa & Thorsten Buc, 2014. "IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4770
    DOI: 10.1038/ncomms4770
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