An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T cell dysfunction

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An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T cell dysfunction

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Title: An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T cell dysfunction
Author: Zhu, Chen; Sakuishi, Kaori; Xiao, Sheng; Sun, Zhiyi; Zaghouani, Sarah; Gu, Guangxiang; Wang, Chao; Tan, Dewar J.; Wu, Chuan; Rangachari, Manu; Pertel, Thomas; Jin, Hyun-Tak; Ahmed, Rafi; Anderson, Ana C.; Kuchroo, Vijay K.

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhu, C., K. Sakuishi, S. Xiao, Z. Sun, S. Zaghouani, G. Gu, C. Wang, et al. 2015. “An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T cell dysfunction.” Nature communications 6 (1): 6072. doi:10.1038/ncomms7072. http://dx.doi.org/10.1038/ncomms7072.
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Abstract: SUMMARY The inhibitory receptor 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 signaling pathways that drive Tim-3 expression. Here, we demonstrate that IL-27 induces NFIL3, which promotes permissive chromatin remodeling 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 signaling axis is crucial for the induction of Tim-3 in vivo. IL-27-conditioned Th1 cells exhibit reduced effector function and are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3 dependent. In contrast, tumor-infiltrating lymphocytes (TILs) from IL-27R−/− mice exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional phenotype, resulting in better tumor growth control. Thus, our data identify an IL-27/NFIL3 signaling axis as a key regulator of effector T cell responses via induction of Tim-3, IL-10, and T cell dysfunction.
Published Version: doi:10.1038/ncomms7072
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311884/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820870
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