Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis
Year: 2025
Type: article
Abstract: Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T H 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 H 2 phenotype. In humans, SERPINB3 reactivity was specifically associated with “eczematized psoriasis” (EczPso), a subtype marked by T H 2/T H 17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T H 2/T H 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.
Source: Science Advances
Authors: Manja Jargosch, Jomy Kuruvila, Emanuele Scala, Johannes Grosch, Jessica Eigemann, Sophia Wasserer, Shalva Lekiashvili, Nico Trautwein, Daniel Johannes Kowalewski, Alexander Böhner, Yigit Köseoglu, Christina Hillig, Jenny Thomas, Felix Lauffer, Carsten B. Schmidt-Weber, Michael P. Menden, Juliane S. Walz, Susanne Kaesler, Stefanie Eyerich, Simon Blank, Hans-Georg Rammensee, Tilo Biedermann, Kilian Eyerich, Zsuzsanna Kurgyis, Lena K. Freudenmann, Natalie Garzorz-Stark
Institutions: Helmholtz Munich, Technical University of Munich, University of Freiburg, University Medical Center Freiburg, Karolinska Institutet, LMU Klinikum, Ludwig-Maximilians-Universität München, University of Tübingen, Institute of Computational Biology, German Center for Lung Research, The University of Melbourne, German Cancer Research Center, Universitätsklinikum Tübingen
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4415440530