TY  - JOUR
AU  - Jargosch, Manja
AU  - Kuruvila, Jomy
AU  - Scala, Emanuele
AU  - Grosch, Johannes
AU  - Eigemann, Jessica
AU  - Wasserer, Sophia
AU  - Lekiashvili, Shalva
AU  - Trautwein, Nico
AU  - Kowalewski, Daniel Johannes
AU  - Böhner, Alexander
AU  - Köseoglu, Yigit
AU  - Hillig, Christina
AU  - Thomas, Jenny
AU  - Lauffer, Felix
AU  - Schmidt-Weber, Carsten B
AU  - Menden, Michael P
AU  - Walz, Juliane
AU  - Kaesler, Susanne
AU  - Eyerich, Stefanie
AU  - Blank, Simon
AU  - Rammensee, Hans-Georg
AU  - Biedermann, Tilo
AU  - Eyerich, Kilian
AU  - Kurgyis, Zsuzsanna
AU  - Freudenmann, Lena
AU  - Garzorz-Stark, Natalie
TI  - Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis.
JO  - Science advances
VL  - 11
IS  - 43
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DKFZ-2025-02195
SP  - eadx0637
PY  - 2025
AB  - 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.
KW  - Psoriasis: immunology
KW  - Psoriasis: metabolism
KW  - Psoriasis: pathology
KW  - Serpins: immunology
KW  - Serpins: metabolism
KW  - Serpins: genetics
KW  - Autoantigens: immunology
KW  - Autoantigens: metabolism
KW  - Animals
KW  - Humans
KW  - Mice
KW  - Th17 Cells: immunology
KW  - Th17 Cells: metabolism
KW  - Disease Models, Animal
KW  - Th2 Cells: immunology
KW  - Th2 Cells: metabolism
KW  - Female
KW  - Skin: immunology
KW  - Skin: pathology
KW  - Skin: metabolism
KW  - Antigens, Neoplasm
KW  - Serpins (NLM Chemicals)
KW  - Autoantigens (NLM Chemicals)
KW  - squamous cell carcinoma-related antigen (NLM Chemicals)
KW  - Antigens, Neoplasm (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41124250
C2  - pmc:PMC12542932
DO  - DOI:10.1126/sciadv.adx0637
UR  - https://inrepo02.dkfz.de/record/305511
ER  -