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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.S.* ; Kaesler, S.* ; Eyerich, S. ; Blank, S. ; Rammensee, H.G.* ; Biedermann, T.* ; Eyerich, K.* ; Kurgyis, Z.* ; Freudenmann, L.K.* ; Garzorz-Stark, N.*

Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.

Sci. Adv. 11:eadx0637 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Quellenangaben Volume: 11, Issue: 43, Pages: , Article Number: eadx0637 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
Research field(s) Allergy
Enabling and Novel Technologies
PSP Element(s) G-505490-001
G-505400-001
G-554700-001
Scopus ID 105019727952
PubMed ID 41124250
Erfassungsdatum 2025-10-23