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Meister M, Papatriantafyllou M, Nordström V, et al. Dickkopf-3, a tissue-derived modulator of local T-cell responses. Front Immunol. 2015;6:78doi: 10.3389/fimmu.2015.00078.
Meister, M., Papatriantafyllou, M., Nordström, V., Kumar, V., Ludwig, J., Lui, K. O., Boyd, A. S., Popovic, Z. V., Fleming, T. H., Moldenhauer, G., Nawroth, P. P., Gröne, H. J., Waldmann, H., Oelert, T., & Arnold, B. (2015). Dickkopf-3, a tissue-derived modulator of local T-cell responses. Frontiers in immunology, 678. https://doi.org/10.3389/fimmu.2015.00078
Meister, Michael, et al. "Dickkopf-3, a tissue-derived modulator of local T-cell responses." Frontiers in immunology vol. 6 (2015): 78. doi: https://doi.org/10.3389/fimmu.2015.00078
Meister M, Papatriantafyllou M, Nordström V, Kumar V, Ludwig J, Lui KO, Boyd AS, Popovic ZV, Fleming TH, Moldenhauer G, Nawroth PP, Gröne HJ, Waldmann H, Oelert T, Arnold B. Dickkopf-3, a tissue-derived modulator of local T-cell responses. Front Immunol. 2015 Feb 24;6:78. doi: 10.3389/fimmu.2015.00078. eCollection 2015. PMID: 25759692; PMCID: PMC4338807.
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Front Immunol. 2015 Feb 24;6:78. doi: 10.3389/fimmu.2015.00078. eCollection 2015.

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

Frontiers in immunology

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, Bernd Arnold

Affiliations

  1. Department of Molecular Immunology, German Cancer Research Center , Heidelberg , Germany.
  2. Department of Molecular Pathology, German Cancer Research Center , Heidelberg , Germany.
  3. Department of Medicine I and Clinical Chemistry, University of Heidelberg , Heidelberg , Germany.
  4. Therapeutic Immunology Group, Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
  5. Department of Molecular Pathology, German Cancer Research Center , Heidelberg , Germany ; Department of Pathology, University Medical Center Mannheim, University of Heidelberg , Mannheim , Germany.

PMID: 25759692 PMCID: PMC4338807 DOI: 10.3389/fimmu.2015.00078

Abstract

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.

Keywords: Dickkopf-3; T cells; autoimmunity; immune privilege; transplantation

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