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

Frontiers in Immunology
Michael MeisterBernd Arnold

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-de...Continue Reading

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Citations

Dec 22, 2015·Osteoarthritis and Cartilage·Sarah J B SnellingIan M Clark
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May 8, 2021·European Journal of Immunology·Herman Waldmann
Dec 11, 2021·Journal of Leukocyte Biology·Min Hee ParkWook-Jin Chae

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Datasets Mentioned

BETA
GM-CSF-APC

Methods Mentioned

BETA
transgenic
FCS
PCR
flow cytometry
ELISA

Software Mentioned

FACS Diva
GraphPad Prism
FlowJo

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