Journal article
IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4 T cells by inducing Blimp1
C Heinemann, S Heink, F Petermann, A Vasanthakumar, V Rothhammer, E Doorduijn, M Mitsdoerffer, C Sie, OP Da Costa, T Buch, B Hemmer, M Oukka, A Kallies, T Korn
Nature Communications | Published : 2014
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-inflammato..
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Awarded by Australian Research Council
Funding Acknowledgements
We would like to thank Reinhard Obst for helping with microarray data analysis, and Malte Claussen for helping with initial experiments, as well as Svenja Woeste and Veronika Husterer for skilful technical assistance. S.H. was supported by the Gemeinnutzige Hertie Stiftung. M.M. received intramural funding by the Klinikum rechts der Isar (KKF). C.S. holds a PHD fellowship from Boehringer Ingelheim Fonds. A.K. was supported by grants and fellowships from the National Health and Medical Research Council of Australia, the Australian Research Council and the Sylvia and Charles Viertel Foundation. This study was partially made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. T.K. is the recipient of a Heisenberg award by the Deutsche Forschungsgemeinschaft (DFG, KO2964/3-2). This work was supported by the DFG (SFB1054/B06, TR128/A06, A07).