IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1 - PubMed (original) (raw)

Sylvia Heink 1, Franziska Petermann 2, Ajithkumar Vasanthakumar 3, Veit Rothhammer 2, Elien Doorduijn 3, Meike Mitsdoerffer 2, Christopher Sie 2, Olivia Prazeres da Costa 4, Thorsten Buch 4, Bernhard Hemmer 5, Mohamed Oukka 6, Axel Kallies 3, Thomas Korn 5

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• PMID: 24796719
• DOI: 10.1038/ncomms4770

Free article

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

Christina Heinemann et al. Nat Commun. 2014.

Free article

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.

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