Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis
Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T<sub>H</sub>17) 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 T<sub>H</sub>2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by T<sub>H</sub>2/T<sub>H</sub>17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T<sub>H</sub>2/T<sub>H</sub>17 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.
Authors
- Alexander Böhner (ORCID: https://orcid.org/0000-0003-1590-0805)
- Susanne Kaesler (ORCID: https://orcid.org/0000-0002-4029-7895)
- Sophia Wasserer
- Felix Lauffer (ORCID: https://orcid.org/0000-0002-1992-2836)
- Christina Hillig (ORCID: https://orcid.org/0000-0001-7447-547X)
- Natalie Garzorz‐Stark (ORCID: https://orcid.org/0000-0002-7409-7883)
- Jenny Thomas (ORCID: https://orcid.org/0000-0002-6386-7352)
- Nico Trautwein (ORCID: https://orcid.org/0000-0003-3292-8850)
- Lena Katharina Freudenmann (ORCID: https://orcid.org/0000-0002-9827-4979)
- Michael P. Menden (ORCID: https://orcid.org/0000-0003-0267-5792)
- Zsuzsanna Kurgyis (ORCID: https://orcid.org/0000-0002-3958-4205)
- Stefanie Eyerich (ORCID: https://orcid.org/0000-0002-1166-2355)
- Emanuele Scala (ORCID: https://orcid.org/0000-0001-6848-3262)
- Shalva Lekiashvili (ORCID: https://orcid.org/0000-0002-3579-2824)
- Tilo Biedermann (ORCID: https://orcid.org/0000-0002-5352-5105)
- Simon Blank (ORCID: https://orcid.org/0000-0002-5649-1078)
- Johannes Grosch (ORCID: https://orcid.org/0000-0001-8572-4267)
- Carsten B. Schmidt‐Weber (ORCID: https://orcid.org/0000-0002-3203-8084)
- Juliane S. Walz (ORCID: https://orcid.org/0000-0001-6404-7391)
- Manja Jargosch (ORCID: https://orcid.org/0000-0001-6051-4036)
- Daniel J. Kowalewski (ORCID: https://orcid.org/0000-0003-0482-9927)
- Hans‐Georg Rammensee (ORCID: https://orcid.org/0000-0003-1614-2647)
- Kilian Eyerich (ORCID: https://orcid.org/0000-0003-0094-2674)
- Jessica Eigemann
- Yigit Köseoglu
- Jomy Kuruvila (ORCID: https://orcid.org/0009-0009-0840-6826)
Institutions
- Biotechnology Institute (US)
- The University of Melbourne (AU)
- German Cancer Research Center (DE)
- University Medical Center Freiburg (DE)
- Center for Environmental Health (US)
- Karolinska Institutet (SE)
- Helmholtz Zentrum München (DE)
- LMU Klinikum (DE)
- German Center for Lung Research (DE)
- Technical University of Munich (DE)
- University of Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Advances
- Published
- 2025-10-22
- DOI
- https://doi.org/10.1126/sciadv.adx0637
- Citations
- 1
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.80