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Chopra, S.* ; Zeitvogel, J.* ; Traidl, S.* ; Klug, I.* ; Rodriguez, E. ; Harder, I.* ; Lieb, W.* ; Weidinger, S.* ; Schulz, T.F.* ; Sodeik, B.* ; Döhner, K.* ; Roesner, L.M.* ; Werfel, T.*

Collagen XXIII (COL23A1): A novel risk factor for eczema herpeticum.

J. Allergy Clin. Immunol., DOI: 10.1016/j.jaci.2025.06.011 (2025)
DOI PMC
BACKGROUND: Eczema herpeticum (EH) is a potentially life-threatening disseminated skin infection caused by herpes simplex virus (HSV) in a subset of atopic dermatitis (AD) patients. The occurrence of EH in a subset of AD patients and its frequent recurrence imply the importance of genetic factors in its pathogenesis. OBJECTIVE: We aimed to identify novel genetic risk factors for EH and to study their impact on HSV-1 infection. METHODS: Using whole exome sequencing we identified a heterozygous single nucleotide polymorphism (SNP) in the COL23A1 gene (encoding Collagen type XXIII alpha 1 chain or COL23A1) that was associated with EH and validated it by PCR in a larger cohort. We studied the effect of upregulated COL23A1 expression on HSV-1 infection in primary keratinocytes and HaCaT cells and performed bulk RNA sequencing to address the underlying mechanism. RESULTS: EH-patient-derived primary keratinocytes carrying this heterozygous SNP rs2973744 had elevated COL23A1 mRNA and protein levels as well as an increased susceptibility to HSV-1. Increasing the COL23A1 levels experimentally enhanced HSV-1 infection in human keratinocytes. COL23A1 overexpression elevated syndecan-1 and nectin-1 levels on the cell surface, which are HSV-1 attachment and entry factors, respectively, and downregulated genes involved in antiviral responses such as IL1R1, IL32, TLR4, IRF1, S100A9, C3, and CFH. CONCLUSION: The SNP rs2973744 enhances COL23A1 expression in ADEH+-derived keratinocytes. Upregulation of COL23A1 promotes HSV-1 infection presumably by upregulating the HSV-1 attachment and entry factors syndecan-1 and nectin-1 on the cell surface and attenuating antiviral responses of keratinocytes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Atopic Dermatitis ; Col23a1 ; Hsv-1 ; Eczema Herpeticum ; Keratinocytes
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)