TY  - JOUR
A1  - Ritter, Julia
A1  - Zimmermann, Karin
A1  - Jöhrens, Korinna
A1  - Mende, Stefanie
A1  - Seegebarth, Anke
A1  - Siegmund, Britta
A1  - Hennig, Steffen
A1  - Todorova, Kremena
A1  - Rosenwald, Andreas
A1  - Daum, Severin
A1  - Hummel, Michael
A1  - Schumann, Michael
T1  - T-cell repertoires in refractory coeliac disease
JF  - Gut
N2  - Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCR beta rearrangements, which was significantly higher than in controls (6.8%; p<0.01) or RCD type I (6.7%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.
KW  - Intestinal Intraepithelial Lymphocy
KW  - Delta Repertoire
KW  - Lymphoma
KW  - Usage
KW  - Clonality
KW  - Sprue
KW  - Chains
KW  - Design
KW  - Epitope
KW  - Frequency
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226350
VL  - 67
IS  - 4
ER  - 
TY  - JOUR
A1  - Wu, Hao
A1  - Reimann, Sabine
A1  - Siddiqui, Sophiya
A1  - Haag, Rainer
A1  - Siegmund, Britta
A1  - Dernedde, Jens
A1  - Glauben, Rainer
T1  - dPGS Regulates the Phenotype of Macrophages via Metabolic Switching
JF  - Macromolecular Bioscience
N2  - The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L‐/P‐selectin or complement proteins leading to well described anti‐inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL‐10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro‐inflammatory phenotype in a metabolic pathway‐dependent manner.
KW  - infection
KW  - macrophage polarization
KW  - MCP1
KW  - metabolic switch
KW  - polyglycerol sulfates
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212711
VL  - 19
IS  - 12
ER  -