Journal Article

DKFZ-2025-02195

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.

Jargosch, M. ; Kuruvila, J. ; Scala, E. ; Grosch, J. ; Eigemann, J. ; Wasserer, S. ; Lekiashvili, S. ; Trautwein, N. ; Kowalewski, D. J. ; Böhner, A. ; Köseoglu, Y. ; Hillig, C. ; Thomas, J. ; Lauffer, F. ; Schmidt-Weber, C. B. ; Menden, M. P. ; Walz, J.DKFZ* ; Kaesler, S. ; Eyerich, S. ; Blank, S. ; Rammensee, H.-G.DKFZ* ; Biedermann, T. ; Eyerich, K. ; Kurgyis, Z. ; Freudenmann, L.DKFZ* ; Garzorz-Stark, N.

2025
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.adx0637

Abstract: Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (TH17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a TH2 phenotype. In humans, SERPINB3 reactivity was specifically associated with 'eczematized psoriasis' (EczPso), a subtype marked by TH2/TH17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined TH2/TH17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.

Keyword(s): Psoriasis: immunology (MeSH) ; Psoriasis: metabolism (MeSH) ; Psoriasis: pathology (MeSH) ; Serpins: immunology (MeSH) ; Serpins: metabolism (MeSH) ; Serpins: genetics (MeSH) ; Autoantigens: immunology (MeSH) ; Autoantigens: metabolism (MeSH) ; Animals (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Th17 Cells: immunology (MeSH) ; Th17 Cells: metabolism (MeSH) ; Disease Models, Animal (MeSH) ; Th2 Cells: immunology (MeSH) ; Th2 Cells: metabolism (MeSH) ; Female (MeSH) ; Skin: immunology (MeSH) ; Skin: pathology (MeSH) ; Skin: metabolism (MeSH) ; Antigens, Neoplasm (MeSH) ; Serpins ; Autoantigens ; squamous cell carcinoma-related antigen ; Antigens, Neoplasm

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Tübingen (TU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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