Canonical Wnt signaling negatively modulates regulatory T cell function.
| Autor: | van Loosdregt J; Department of Immunology, University Medical Center Utrecht, Utrecht 3584EA, The Netherlands., Fleskens V, Tiemessen MM, Mokry M, van Boxtel R, Meerding J, Pals CE, Kurek D, Baert MR, Delemarre EM, Gröne A, Koerkamp MJ, Sijts AJ, Nieuwenhuis EE, Maurice MM, van Es JH, Ten Berge D, Holstege FC, Staal FJ, Zaiss DM, Prakken BJ, Coffer PJ |
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| Jazyk: | angličtina |
| Zdroj: | Immunity [Immunity] 2013 Aug 22; Vol. 39 (2), pp. 298-310. Date of Electronic Publication: 2013 Aug 15. |
| DOI: | 10.1016/j.immuni.2013.07.019 |
| Abstrakt: | Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both in vitro and in vivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector T cells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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