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Dickkopf-3, a tissue-derived modulator of local T-cell responses

The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T-cell responses in peripheral tissues are poorly characterized....

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Main Authors: Meister, Michael (Author) , Papatriantafyllou, Maria (Author) , Nordström, Viola (Author) , Kumar, Varun (Author) , Ludwig, Julia (Author) , Popovic, Zoran V. (Author) , Fleming, Thomas (Author) , Moldenhauer, Gerhard (Author) , Nawroth, Peter Paul (Author) , Gröne, Hermann-Josef (Author) , Oelert, Thilo (Author) , Arnold, Bernd (Author)
Format: Article (Journal)
Language:English
Published: 24 February 2015
In: Frontiers in immunology
Year: 2015, Volume: 6, Pages: 1-13
ISSN:1664-3224
DOI:10.3389/fimmu.2015.00078
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fimmu.2015.00078
Verlag, kostenfrei, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338807/
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Author Notes:Michael Meister, Maria Papatriantafyllou, Viola Nordström, Varun Kumar, Julia Ludwig, Kathy O. Lui, Ashleigh S. Boyd, Zoran V. Popovic, Thomas Henry Fleming, Gerhard Moldenhauer, Peter P. Nawroth, Hermann-Josef Gröne, Herman Waldmann, Thilo Oelert, and Bernd Arnold
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Summary:The adaptive immune system protects organisms from harmful environmental insults. In parallel, regulatory mechanisms control immune responses in order to assure preservation of organ integrity. Yet, molecules involved in the control of T-cell responses in peripheral tissues are poorly characterized. Here, we investigated the function of Dickkopf-3 in the modulation of local T-cell reactivity. Dkk3 is a secreted, mainly tissue-derived protein with highest expression in organs considered as immune-privileged such as the eye, embryo, placenta, and brain. While T-cell development and activation status in naïve Dkk3-deficient mice was comparable to littermate controls, we found that Dkk3 contributes to the immunosuppressive microenvironment that protects transplanted, class-I mismatched embryoid bodies from T-cell-mediated rejection. Moreover, genetic deletion or antibody-mediated neutralization of Dkk3 led to an exacerbated experimental autoimmune encephalomyelitis (EAE). This phenotype was accompanied by a change of T-cell polarization displayed by an increase of IFNγ-producing T cells within the central nervous system. In the wild-type situation, Dkk3 expression in the brain was up-regulated during the course of EAE in an IFNγ-dependent manner. In turn, Dkk3 decreased IFNγ activity and served as part of a negative feedback mechanism. Thus, our findings suggest that Dkk3 functions as a tissue-derived modulator of local CD4+ and CD8+ T-cell responses.
Item Description:Gesehen am 17.11.2017
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2015.00078

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