eprintid: 25666
rev_number: 17
eprint_status: archive
userid: 4118
dir: disk0/00/02/56/66
datestamp: 2020-05-27 08:07:32
lastmod: 2020-06-02 10:52:53
status_changed: 2020-05-27 08:07:32
type: doctoralThesis
metadata_visibility: show
creators_name: Link, Corinna
title: Analysis of annexin-mediated antigen-specific
immunosuppression
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
cterms_swd: Immunologie
cterms_swd: Autoimmunkrankheiten
cterms_swd: Toleranz
abstract: Apoptotic cells mediate the development of tolerogenic dendritic cells (DC) and thus facilitate
the induction and maintenance of peripheral tolerance. Our group investigated the
influence of apoptotic cells on DC and identified the cell surface exposure of the evolutionary
conserved annexin core domain (Anx) as a specific signal which antagonises Toll-like
receptor (TLR) signalling.
This study examined whether the tolerogenic capacity of Anx can be exploited to downregulate
antigen-specific immune responses to the model antigen ovalbumin (Ova). The
treatment of bone marrow-derived dendritic cells (BMDC) with soluble Anx prior to Ova
administration or the treatment with beads harbouring Anx as well as Ova attenuated the
response of Ova-specific OT-II Tcells. The co-culture of treated DC and Tcells resulted
in an anergy-like phenotype characterised by reduced proliferation and cytokine secretion.
The anti-inflammatory effects of Anx are mediated through DC by yet unknown mechanisms.
Anx did not lead to the tolerogenic DC phenotype described to be induced
by apoptotic cells and also the previously reported suppression of anti-inflammatory cytokines
by Anx was dispensable for the effect on Tcells. However, this study revealed
enhanced production od reactive oxygen species (ROS) in BMDC in response to Anx
which might affect the DC/Tcell interactions.
Although the underlying mechanisms remain to be elucidated, this study demonstrates
that Anx can be used as a tool to generate a particle-based antigen delivery system that
promotes antigen-specific immunosuppression. Such Anx-particles may be a new therapeutic
approach for the treatment of autoimmune disease.
date: 2020
id_scheme: DOI
id_number: 10.11588/heidok.00025666
ppn_swb: 1699188335
own_urn: urn:nbn:de:bsz:16-heidok-256662
date_accepted: 2018-11-21
advisor: HASH(0x55de57982d90)
language: eng
bibsort: LINKCORINNANALYSISOF2020
full_text_status: public
place_of_pub: Heidelberg
citation:   Link, Corinna  (2020) Analysis of annexin-mediated antigen-specific immunosuppression.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/25666/1/Thesis_CL_pdfa.pdf