IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1
Heinemann C, Heink S, Petermann F, Vasanthakumar A, Rothhammer V, Doorduijn E, Mitsdoerffer M, Sie C, Da Costa OP, Buch T, Hemmer B, Oukka M, Kallies A, Korn T (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Book Volume: 5
Article Number: 3770
DOI: 10.1038/ncomms4770
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-Î 3 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. © 2014 Macmillan Publishers Limited. All rights reserved.
Authors with CRIS profile
Involved external institutions
Technische Universität München (TUM)
Germany (DE)
University of Washington
United States (USA) (US)
Walter and Eliza Hall Institute of Medical Research (WEHI)
Australia (AU)
Germany (DE)
University of Washington
United States (USA) (US)
Walter and Eliza Hall Institute of Medical Research (WEHI)
Australia (AU)
How to cite
APA:
Heinemann, C., Heink, S., Petermann, F., Vasanthakumar, A., Rothhammer, V., Doorduijn, E.,... Korn, T. (2014). IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1. Nature Communications, 5. https://doi.org/10.1038/ncomms4770
MLA:
Heinemann, Christina, et al. "IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1." Nature Communications 5 (2014).
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