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Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level

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Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level. / Hagen, Sven Hendrik; Henseling, Florian; Hennesen, Jana; Savel, Hélène; Delahaye, Solenne; Richert, Laura; Ziegler, Susanne Maria; Altfeld, Marcus.

In: CELL REP, Vol. 33, No. 10, 108485, 08.12.2020.

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

Harvard

Hagen, SH, Henseling, F, Hennesen, J, Savel, H, Delahaye, S, Richert, L, Ziegler, SM & Altfeld, M 2020, 'Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level', CELL REP, vol. 33, no. 10, 108485. https://doi.org/10.1016/j.celrep.2020.108485

APA

Hagen, S. H., Henseling, F., Hennesen, J., Savel, H., Delahaye, S., Richert, L., Ziegler, S. M., & Altfeld, M. (2020). Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level. CELL REP, 33(10), [108485]. https://doi.org/10.1016/j.celrep.2020.108485

Vancouver

Hagen SH, Henseling F, Hennesen J, Savel H, Delahaye S, Richert L et al. Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level. CELL REP. 2020 Dec 8;33(10). 108485. https://doi.org/10.1016/j.celrep.2020.108485

Bibtex

@article{e3c566bb159d49c088154ebec94a8532,
title = "Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level",
abstract = "Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression patterns. pDCs with biallelic gene expression have significantly higher mRNA levels of the respective genes. Unstimulated pDCs with biallelic TLR7 expression exhibit significantly higher IFNα/β mRNA levels, and IFNα exposure results in significantly increased IFNα/β protein production by pDCs. These results identify unanticipated heterogeneity in escape from XCI of several genes in pDCs and highlight the important contribution of X chromosome factors to sex differences in type I IFN responses, which might explain observed sex differences in human diseases.",
keywords = "Cells, Cultured, Dendritic Cells/immunology, Female, Gene Expression/genetics, Humans, Immunity, Innate/physiology, Interferon Type I/metabolism, Male, RNA, Messenger/metabolism, Sex Characteristics, Sex Factors, Signal Transduction/genetics, Toll-Like Receptor 7/metabolism, X Chromosome Inactivation/genetics",
author = "Hagen, {Sven Hendrik} and Florian Henseling and Jana Hennesen and H{\'e}l{\`e}ne Savel and Solenne Delahaye and Laura Richert and Ziegler, {Susanne Maria} and Marcus Altfeld",
note = "Copyright {\textcopyright} 2020 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = dec,
day = "8",
doi = "10.1016/j.celrep.2020.108485",
language = "English",
volume = "33",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "10",

}

RIS

TY - JOUR

T1 - Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level

AU - Hagen, Sven Hendrik

AU - Henseling, Florian

AU - Hennesen, Jana

AU - Savel, Hélène

AU - Delahaye, Solenne

AU - Richert, Laura

AU - Ziegler, Susanne Maria

AU - Altfeld, Marcus

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/12/8

Y1 - 2020/12/8

N2 - Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression patterns. pDCs with biallelic gene expression have significantly higher mRNA levels of the respective genes. Unstimulated pDCs with biallelic TLR7 expression exhibit significantly higher IFNα/β mRNA levels, and IFNα exposure results in significantly increased IFNα/β protein production by pDCs. These results identify unanticipated heterogeneity in escape from XCI of several genes in pDCs and highlight the important contribution of X chromosome factors to sex differences in type I IFN responses, which might explain observed sex differences in human diseases.

AB - Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression patterns. pDCs with biallelic gene expression have significantly higher mRNA levels of the respective genes. Unstimulated pDCs with biallelic TLR7 expression exhibit significantly higher IFNα/β mRNA levels, and IFNα exposure results in significantly increased IFNα/β protein production by pDCs. These results identify unanticipated heterogeneity in escape from XCI of several genes in pDCs and highlight the important contribution of X chromosome factors to sex differences in type I IFN responses, which might explain observed sex differences in human diseases.

KW - Cells, Cultured

KW - Dendritic Cells/immunology

KW - Female

KW - Gene Expression/genetics

KW - Humans

KW - Immunity, Innate/physiology

KW - Interferon Type I/metabolism

KW - Male

KW - RNA, Messenger/metabolism

KW - Sex Characteristics

KW - Sex Factors

KW - Signal Transduction/genetics

KW - Toll-Like Receptor 7/metabolism

KW - X Chromosome Inactivation/genetics

U2 - 10.1016/j.celrep.2020.108485

DO - 10.1016/j.celrep.2020.108485

M3 - SCORING: Journal article

C2 - 33296655

VL - 33

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 10

M1 - 108485

ER -