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@ARTICLE{Jargosch:305511,
author = {M. Jargosch and J. Kuruvila and E. Scala and J. Grosch and
J. Eigemann and S. Wasserer and S. Lekiashvili and N.
Trautwein and D. J. Kowalewski and A. Böhner and Y.
Köseoglu and C. Hillig and J. Thomas and F. Lauffer and C.
B. Schmidt-Weber and M. P. Menden and J. Walz$^*$ and S.
Kaesler and S. Eyerich and S. Blank and H.-G. Rammensee$^*$
and T. Biedermann and K. Eyerich and Z. Kurgyis and L.
Freudenmann$^*$ and N. Garzorz-Stark},
title = {{I}mmunopeptidome analysis reveals {SERPINB}3 as an
autoantigen driving eczematized psoriasis.},
journal = {Science advances},
volume = {11},
number = {43},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DKFZ-2025-02195},
pages = {eadx0637},
year = {2025},
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.},
keywords = {Psoriasis: immunology / Psoriasis: metabolism / Psoriasis:
pathology / Serpins: immunology / Serpins: metabolism /
Serpins: genetics / Autoantigens: immunology / Autoantigens:
metabolism / Animals / Humans / Mice / Th17 Cells:
immunology / Th17 Cells: metabolism / Disease Models, Animal
/ Th2 Cells: immunology / Th2 Cells: metabolism / Female /
Skin: immunology / Skin: pathology / Skin: metabolism /
Antigens, Neoplasm / Serpins (NLM Chemicals) / Autoantigens
(NLM Chemicals) / squamous cell carcinoma-related antigen
(NLM Chemicals) / Antigens, Neoplasm (NLM Chemicals)},
cin = {TU01},
ddc = {500},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41124250},
pmc = {pmc:PMC12542932},
doi = {10.1126/sciadv.adx0637},
url = {https://inrepo02.dkfz.de/record/305511},
}