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Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms

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Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. / Sebode, Marcial; Peiseler, Moritz; Franke, Björn; Schwinge, Dorothee; Schoknecht, Tanja; Wortmann, Frederike; Quaas, Alexander; Petersen, Britt-Sabina; Ellinghaus, Eva; Baron, Udo; Olek, Sven; Wiegard, Christiane; Weiler-Normann, Christina; Lohse, Ansgar W; Herkel, Johannes; Schramm, Christoph.

In: J HEPATOL, Vol. 60, No. 5, 01.05.2014, p. 1010-6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sebode, M, Peiseler, M, Franke, B, Schwinge, D, Schoknecht, T, Wortmann, F, Quaas, A, Petersen, B-S, Ellinghaus, E, Baron, U, Olek, S, Wiegard, C, Weiler-Normann, C, Lohse, AW, Herkel, J & Schramm, C 2014, 'Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms', J HEPATOL, vol. 60, no. 5, pp. 1010-6. https://doi.org/10.1016/j.jhep.2013.12.027

APA

Sebode, M., Peiseler, M., Franke, B., Schwinge, D., Schoknecht, T., Wortmann, F., Quaas, A., Petersen, B-S., Ellinghaus, E., Baron, U., Olek, S., Wiegard, C., Weiler-Normann, C., Lohse, A. W., Herkel, J., & Schramm, C. (2014). Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. J HEPATOL, 60(5), 1010-6. https://doi.org/10.1016/j.jhep.2013.12.027

Vancouver

Sebode M, Peiseler M, Franke B, Schwinge D, Schoknecht T, Wortmann F et al. Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. J HEPATOL. 2014 May 1;60(5):1010-6. https://doi.org/10.1016/j.jhep.2013.12.027

Bibtex

@article{bc5353acfb0a439893f9a9006d37f2a2,
title = "Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms",
abstract = "BACKGROUND & AIMS: Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associate their numbers with relevant gene polymorphisms.METHODS: Treg frequency in blood was assessed by staining for CD4(+)CD25(high)FOXP3(+)CD127(low) lymphocytes and determination of Treg-specific FOXP3 gene locus demethylation. Single nucleotide polymorphisms (SNP) in the interleukin-2 receptor alpha (IL2RA), the interleukin-2 (IL2) and interleukin-21 (IL21) gene locus were analysed. Liver biopsies taken at the time of diagnosis were stained for FOXP3 and CD3. Treg function was assessed in a CFSE-based suppression assay.RESULTS: The frequency of Treg in peripheral blood of PSC patients was significantly decreased. We confirmed this finding by demonstrating a reduction of non-methylated DNA in the Treg-specific demethylated FOXP3 gene region of peripheral blood cells in PSC patients. Reduced peripheral Treg numbers were significantly associated with homozygosity for the major allele of the SNP {"}rs10905718{"} in the IL2RA gene. Intrahepatic FOXP3(+) cell numbers at the time of initial diagnosis were decreased in PSC as compared to PBC. In addition to reduced numbers, the suppressive capacity of Treg isolated from PSC patients seemed to be impaired as compared to healthy controls.CONCLUSIONS: Our findings indicate that Treg impairment may play a role in the immune dysregulation observed in PSC. Reduced Treg numbers in patients with PSC are associated with polymorphisms in the IL2RA gene.",
author = "Marcial Sebode and Moritz Peiseler and Bj{\"o}rn Franke and Dorothee Schwinge and Tanja Schoknecht and Frederike Wortmann and Alexander Quaas and Britt-Sabina Petersen and Eva Ellinghaus and Udo Baron and Sven Olek and Christiane Wiegard and Christina Weiler-Normann and Lohse, {Ansgar W} and Johannes Herkel and Christoph Schramm",
note = "Copyright {\textcopyright} 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2014",
month = may,
day = "1",
doi = "10.1016/j.jhep.2013.12.027",
language = "English",
volume = "60",
pages = "1010--6",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms

AU - Sebode, Marcial

AU - Peiseler, Moritz

AU - Franke, Björn

AU - Schwinge, Dorothee

AU - Schoknecht, Tanja

AU - Wortmann, Frederike

AU - Quaas, Alexander

AU - Petersen, Britt-Sabina

AU - Ellinghaus, Eva

AU - Baron, Udo

AU - Olek, Sven

AU - Wiegard, Christiane

AU - Weiler-Normann, Christina

AU - Lohse, Ansgar W

AU - Herkel, Johannes

AU - Schramm, Christoph

N1 - Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - BACKGROUND & AIMS: Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associate their numbers with relevant gene polymorphisms.METHODS: Treg frequency in blood was assessed by staining for CD4(+)CD25(high)FOXP3(+)CD127(low) lymphocytes and determination of Treg-specific FOXP3 gene locus demethylation. Single nucleotide polymorphisms (SNP) in the interleukin-2 receptor alpha (IL2RA), the interleukin-2 (IL2) and interleukin-21 (IL21) gene locus were analysed. Liver biopsies taken at the time of diagnosis were stained for FOXP3 and CD3. Treg function was assessed in a CFSE-based suppression assay.RESULTS: The frequency of Treg in peripheral blood of PSC patients was significantly decreased. We confirmed this finding by demonstrating a reduction of non-methylated DNA in the Treg-specific demethylated FOXP3 gene region of peripheral blood cells in PSC patients. Reduced peripheral Treg numbers were significantly associated with homozygosity for the major allele of the SNP "rs10905718" in the IL2RA gene. Intrahepatic FOXP3(+) cell numbers at the time of initial diagnosis were decreased in PSC as compared to PBC. In addition to reduced numbers, the suppressive capacity of Treg isolated from PSC patients seemed to be impaired as compared to healthy controls.CONCLUSIONS: Our findings indicate that Treg impairment may play a role in the immune dysregulation observed in PSC. Reduced Treg numbers in patients with PSC are associated with polymorphisms in the IL2RA gene.

AB - BACKGROUND & AIMS: Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associate their numbers with relevant gene polymorphisms.METHODS: Treg frequency in blood was assessed by staining for CD4(+)CD25(high)FOXP3(+)CD127(low) lymphocytes and determination of Treg-specific FOXP3 gene locus demethylation. Single nucleotide polymorphisms (SNP) in the interleukin-2 receptor alpha (IL2RA), the interleukin-2 (IL2) and interleukin-21 (IL21) gene locus were analysed. Liver biopsies taken at the time of diagnosis were stained for FOXP3 and CD3. Treg function was assessed in a CFSE-based suppression assay.RESULTS: The frequency of Treg in peripheral blood of PSC patients was significantly decreased. We confirmed this finding by demonstrating a reduction of non-methylated DNA in the Treg-specific demethylated FOXP3 gene region of peripheral blood cells in PSC patients. Reduced peripheral Treg numbers were significantly associated with homozygosity for the major allele of the SNP "rs10905718" in the IL2RA gene. Intrahepatic FOXP3(+) cell numbers at the time of initial diagnosis were decreased in PSC as compared to PBC. In addition to reduced numbers, the suppressive capacity of Treg isolated from PSC patients seemed to be impaired as compared to healthy controls.CONCLUSIONS: Our findings indicate that Treg impairment may play a role in the immune dysregulation observed in PSC. Reduced Treg numbers in patients with PSC are associated with polymorphisms in the IL2RA gene.

U2 - 10.1016/j.jhep.2013.12.027

DO - 10.1016/j.jhep.2013.12.027

M3 - SCORING: Journal article

C2 - 24412607

VL - 60

SP - 1010

EP - 1016

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 5

ER -