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Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus

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Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus. / Franz, Henriette; Rathod, Maitreyi; Zimmermann, Aude; Stüdle, Chiara; Beyersdorfer, Vivien; Leal-Fischer, Karen; Hanns, Pauline; Cunha, Tomás; Didona, Dario; Hertl, Michael; Scheibe, Marion; Butter, Falk; Schmidt, Enno; Spindler, Volker.

in: NAT COMMUN, Jahrgang 15, Nr. 1, 14.09.2024, S. 8044.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Franz, H, Rathod, M, Zimmermann, A, Stüdle, C, Beyersdorfer, V, Leal-Fischer, K, Hanns, P, Cunha, T, Didona, D, Hertl, M, Scheibe, M, Butter, F, Schmidt, E & Spindler, V 2024, 'Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus', NAT COMMUN, Jg. 15, Nr. 1, S. 8044. https://doi.org/10.1038/s41467-024-51747-2

APA

Franz, H., Rathod, M., Zimmermann, A., Stüdle, C., Beyersdorfer, V., Leal-Fischer, K., Hanns, P., Cunha, T., Didona, D., Hertl, M., Scheibe, M., Butter, F., Schmidt, E., & Spindler, V. (2024). Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus. NAT COMMUN, 15(1), 8044. https://doi.org/10.1038/s41467-024-51747-2

Vancouver

Franz H, Rathod M, Zimmermann A, Stüdle C, Beyersdorfer V, Leal-Fischer K et al. Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus. NAT COMMUN. 2024 Sep 14;15(1):8044. https://doi.org/10.1038/s41467-024-51747-2

Bibtex

@article{ad5c6c4565334087b8113579415ab48d,
title = "Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus",
abstract = "Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.",
keywords = "Humans, Pemphigus/metabolism, Cell Adhesion, Desmoglein 3/metabolism, Animals, Keratinocytes/metabolism, Mice, Kruppel-Like Transcription Factors/metabolism, Autoantibodies/immunology, Desmosomes/metabolism, Disease Models, Animal, Histone Deacetylases/metabolism, Gene Expression Regulation, Promoter Regions, Genetic/genetics, Male",
author = "Henriette Franz and Maitreyi Rathod and Aude Zimmermann and Chiara St{\"u}dle and Vivien Beyersdorfer and Karen Leal-Fischer and Pauline Hanns and Tom{\'a}s Cunha and Dario Didona and Michael Hertl and Marion Scheibe and Falk Butter and Enno Schmidt and Volker Spindler",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = sep,
day = "14",
doi = "10.1038/s41467-024-51747-2",
language = "English",
volume = "15",
pages = "8044",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Unbiased screening identifies regulators of cell-cell adhesion and treatment options in pemphigus

AU - Franz, Henriette

AU - Rathod, Maitreyi

AU - Zimmermann, Aude

AU - Stüdle, Chiara

AU - Beyersdorfer, Vivien

AU - Leal-Fischer, Karen

AU - Hanns, Pauline

AU - Cunha, Tomás

AU - Didona, Dario

AU - Hertl, Michael

AU - Scheibe, Marion

AU - Butter, Falk

AU - Schmidt, Enno

AU - Spindler, Volker

N1 - © 2024. The Author(s).

PY - 2024/9/14

Y1 - 2024/9/14

N2 - Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.

AB - Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.

KW - Humans

KW - Pemphigus/metabolism

KW - Cell Adhesion

KW - Desmoglein 3/metabolism

KW - Animals

KW - Keratinocytes/metabolism

KW - Mice

KW - Kruppel-Like Transcription Factors/metabolism

KW - Autoantibodies/immunology

KW - Desmosomes/metabolism

KW - Disease Models, Animal

KW - Histone Deacetylases/metabolism

KW - Gene Expression Regulation

KW - Promoter Regions, Genetic/genetics

KW - Male

U2 - 10.1038/s41467-024-51747-2

DO - 10.1038/s41467-024-51747-2

M3 - SCORING: Journal article

C2 - 39271654

VL - 15

SP - 8044

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -