Other
15 Authors
- Zhu C,
- Rangachari M,
- Jin HT,
- Zaghouani S,
- Kuchroo VK,
- Tan DJ,
- Sun Z,
- Sakuishi K,
- Gu G,
- Pertel T,
- Ahmed R,
- Wu C,
- Anderson AC,
- Wang C,
- Xiao S
| First Author | Zhu C | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6072 | PubMed ID | 25614966 |
| Mgi Jnum | J:219798 | Mgi Id | MGI:5629766 |
| Doi | 10.1038/ncomms7072 | Citation | Zhu C, et al. (2015) An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. Nat Commun 6:6072 |
| abstractText | The inhibitory receptor T-cell immunoglobulin and mucin domain-3 (Tim-3) has emerged as a critical regulator of the T-cell dysfunction that develops in chronic viral infections and cancers. However, little is known regarding the signalling pathways that drive Tim-3 expression. Here, we demonstrate that interleukin (IL)-27 induces nuclear factor, interleukin 3 regulated (NFIL3), which promotes permissive chromatin remodelling of the Tim-3 locus and induces Tim-3 expression together with the immunosuppressive cytokine IL-10. We further show that the IL-27/NFIL3 signalling axis is crucial for the induction of Tim-3 in vivo. IL-27-conditioned T helper 1 cells exhibit reduced effector function and are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3 dependent. In contrast, tumour-infiltrating lymphocytes from IL-27R(-/-) mice exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional phenotype, resulting in better tumour growth control. Thus, our data identify an IL-27/NFIL3 signalling axis as a key regulator of effector T-cell responses via induction of Tim-3, IL-10 and T-cell dysfunction. |
