Research ExplorerPublicationsIntergenic risk variant rs56258221 skews the fate of naive C...

Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis

Standard

Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis. / Poch, Tobias; Bahn, Jonas; Casar, Christian; Krause, Jenny; Evangelakos, Ioannis; Gilladi, Hilla; Kunzmann, Lilly K; Laschtowitz, Alena; Iuso, Nicola; Schäfer, Anne-Marie; Liebig, Laura A; Steinmann, Silja; Sebode, Marcial; Folseraas, Trine; Engesæter, Lise K; Karlsen, Tom H; Franke, Andre; Metabolic Sciences, Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, Cardiovascular; Schlein, Christian; Galun, Eithan; Huber, Samuel; Lohse, Ansgar W; Gagliani, Nicola; Schwinge, Dorothee; Schramm, Christoph.

In: CELL REP MED, Vol. 5, No. 7, 16.07.2024, p. 101620.

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

Harvard

Poch, T, Bahn, J, Casar, C, Krause, J, Evangelakos, I, Gilladi, H, Kunzmann, LK, Laschtowitz, A, Iuso, N, Schäfer, A-M, Liebig, LA, Steinmann, S, Sebode, M, Folseraas, T, Engesæter, LK, Karlsen, TH, Franke, A, Metabolic Sciences, Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, C, Schlein, C, Galun, E, Huber, S, Lohse, AW, Gagliani, N, Schwinge, D & Schramm, C 2024, 'Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis', CELL REP MED, vol. 5, no. 7, pp. 101620. https://doi.org/10.1016/j.xcrm.2024.101620

APA

Poch, T., Bahn, J., Casar, C., Krause, J., Evangelakos, I., Gilladi, H., Kunzmann, L. K., Laschtowitz, A., Iuso, N., Schäfer, A-M., Liebig, L. A., Steinmann, S., Sebode, M., Folseraas, T., Engesæter, L. K., Karlsen, T. H., Franke, A., Metabolic Sciences, Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, C., Schlein, C., ... Schramm, C. (2024). Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis. CELL REP MED, 5(7), 101620. https://doi.org/10.1016/j.xcrm.2024.101620

Vancouver

Poch T, Bahn J, Casar C, Krause J, Evangelakos I, Gilladi H et al. Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis. CELL REP MED. 2024 Jul 16;5(7):101620. https://doi.org/10.1016/j.xcrm.2024.101620

Bibtex

@article{1053ccfb45ba4d0d91c72106757a72b1,
title = "Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis",
abstract = "Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4+ T (CD4+ TN) cells in people with PSC. Mechanistically, rs56258221 leads to an increased expression of miR4464, in turn causing attenuated translation of BACH2, a major gatekeeper of T cell quiescence. Thereby, the fate of CD4+ TN is skewed toward polarization into pro-inflammatory subsets. Clinically, people with PSC carrying rs56258221 show signs of accelerated disease progression. The data presented here highlight the importance of assigning functional outcomes to disease-associated genetic polymorphisms as potential drivers of diseases.",
author = "Tobias Poch and Jonas Bahn and Christian Casar and Jenny Krause and Ioannis Evangelakos and Hilla Gilladi and Kunzmann, {Lilly K} and Alena Laschtowitz and Nicola Iuso and Anne-Marie Sch{\"a}fer and Liebig, {Laura A} and Silja Steinmann and Marcial Sebode and Trine Folseraas and Enges{\ae}ter, {Lise K} and Karlsen, {Tom H} and Andre Franke and {Metabolic Sciences, Max Delbr{\"u}ck Centre for Molecular Medicine in the Helmholtz Association}, Cardiovascular and Christian Schlein and Eithan Galun and Samuel Huber and Lohse, {Ansgar W} and Nicola Gagliani and Dorothee Schwinge and Christoph Schramm",
note = "Copyright {\textcopyright} 2024 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2024",
month = jul,
day = "16",
doi = "10.1016/j.xcrm.2024.101620",
language = "English",
volume = "5",
pages = "101620",
journal = "CELL REP MED",
issn = "2666-3791",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis

AU - Poch, Tobias

AU - Bahn, Jonas

AU - Casar, Christian

AU - Krause, Jenny

AU - Evangelakos, Ioannis

AU - Gilladi, Hilla

AU - Kunzmann, Lilly K

AU - Laschtowitz, Alena

AU - Iuso, Nicola

AU - Schäfer, Anne-Marie

AU - Liebig, Laura A

AU - Steinmann, Silja

AU - Sebode, Marcial

AU - Folseraas, Trine

AU - Engesæter, Lise K

AU - Karlsen, Tom H

AU - Franke, Andre

AU - Metabolic Sciences, Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, Cardiovascular

AU - Schlein, Christian

AU - Galun, Eithan

AU - Huber, Samuel

AU - Lohse, Ansgar W

AU - Gagliani, Nicola

AU - Schwinge, Dorothee

AU - Schramm, Christoph

N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2024/7/16

Y1 - 2024/7/16

N2 - Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4+ T (CD4+ TN) cells in people with PSC. Mechanistically, rs56258221 leads to an increased expression of miR4464, in turn causing attenuated translation of BACH2, a major gatekeeper of T cell quiescence. Thereby, the fate of CD4+ TN is skewed toward polarization into pro-inflammatory subsets. Clinically, people with PSC carrying rs56258221 show signs of accelerated disease progression. The data presented here highlight the importance of assigning functional outcomes to disease-associated genetic polymorphisms as potential drivers of diseases.

AB - Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4+ T (CD4+ TN) cells in people with PSC. Mechanistically, rs56258221 leads to an increased expression of miR4464, in turn causing attenuated translation of BACH2, a major gatekeeper of T cell quiescence. Thereby, the fate of CD4+ TN is skewed toward polarization into pro-inflammatory subsets. Clinically, people with PSC carrying rs56258221 show signs of accelerated disease progression. The data presented here highlight the importance of assigning functional outcomes to disease-associated genetic polymorphisms as potential drivers of diseases.

U2 - 10.1016/j.xcrm.2024.101620

DO - 10.1016/j.xcrm.2024.101620

M3 - SCORING: Journal article

C2 - 38901430

VL - 5

SP - 101620

JO - CELL REP MED

JF - CELL REP MED

SN - 2666-3791

IS - 7

ER -