IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1
- Author(s)
- Heinemann, C; Heink, S; Petermann, F; Vasanthakumar, A; Rothhammer, V; Doorduijn, E; Mitsdoerffer, M; Sie, C; Prazeres da Costa, O; Buch, T; Hemmer, B; Oukka, M; Kallies, A; Korn, T;
- Journal Title
- Nat Commun
- Publication Type
- Journal 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-gamma 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.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology
- Publisher's Version
- https://doi.org/10.1038/ncomms4770
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Creation Date: 2014-07-09 09:33:57