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

Christina Heinemann, Sylvia Heink, Franziska Petermann, Ajithkumar Vasanthakumar, Veit Rothhammer, Elien Doorduijn, Meike Mitsdoerffer, Christopher Sie, Olivia Prazeres da Costa, Thorsten Buch, Bernhard Hemmer, Mohamed Oukka, Axel Kallies () and Thomas Korn ()
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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
Veit Rothhammer: Klinikum rechts der Isar, Technische Universität München
Elien Doorduijn: The Walter and Eliza Hall Institute of Medical Research
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
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
Thomas Korn: Klinikum rechts der Isar, Technische Universität München

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4770

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