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000136090 0247_ $$2doi$$a10.3389/fimmu.2015.00078
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000136090 1001_ $$0P:(DE-He78)aa3ff9fc2739d5cb7f822cbd7c1e39c9$$aMeister, Michael$$b0$$eFirst author$$udkfz
000136090 245__ $$aDickkopf-3, a tissue-derived modulator of local T-cell responses.
000136090 260__ $$aLausanne$$bFrontiers Media$$c2015
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000136090 520__ $$aThe 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.
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000136090 7001_ $$0P:(DE-HGF)0$$aPapatriantafyllou, Maria$$b1
000136090 7001_ $$0P:(DE-He78)9bce4efcbedb17d7b4d0d7832c136faf$$aNordström, Viola$$b2$$udkfz
000136090 7001_ $$aKumar, Varun$$b3
000136090 7001_ $$0P:(DE-He78)ef1ac16ab2fde9280b9c44dfed15848f$$aLudwig, Julia$$b4$$udkfz
000136090 7001_ $$aLui, Kathy O$$b5
000136090 7001_ $$aBoyd, Ashleigh S$$b6
000136090 7001_ $$0P:(DE-He78)659b67be544344052284c48f7d49c7cd$$aPopovic, Zoran$$b7$$udkfz
000136090 7001_ $$aFleming, Thomas Henry$$b8
000136090 7001_ $$0P:(DE-HGF)0$$aMoldenhauer, Gerhard$$b9
000136090 7001_ $$aNawroth, Peter P$$b10
000136090 7001_ $$0P:(DE-He78)00a2ea610aee4a8fca32908fc3d02e91$$aGröne, Hermann-Josef$$b11$$udkfz
000136090 7001_ $$0P:(DE-HGF)0$$aWaldmann, Herman$$b12
000136090 7001_ $$0P:(DE-HGF)0$$aOelert, Thilo$$b13
000136090 7001_ $$0P:(DE-He78)554abc2af2666cc3421cc0d7f6e7b6de$$aArnold, Bernd$$b14$$eLast author$$udkfz
000136090 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2015.00078$$gVol. 6$$p78$$tFrontiers in immunology$$v6$$x1664-3224$$y2015
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