Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrotic remodeling of the skin and internal organs. Fibrotic tissue changes are considered hardly reversible with current therapies, suggesting that new strategies are required to modulate the disease-associated molecular and cellular phenotype to enable regeneration of affected tissues. Here, analyzing skin biopsy samples from patients with SSc who had received CD19-CAR T cell therapy as part of the CASTLE study or named patient use, we demonstrate structural regeneration of SSc skin structure, as evidenced by recovery of skin papillae. Consistent with these histological changes, cyclic in situ hybridization and imaging mass cytometry analyses suggested that fibroblast populations shifted towards a physiological state, both in terms of composition and function. Moreover, we describe signs of vascular repair and changes in epidermal cell function. These results suggest that B cell depletion using CD19-CAR T cell therapy may lead to skin tissue remodeling in SSc and highlight its potential for tissue regeneration in fibrotic diseases.
Authors
- Rafael Schmid (ORCID: https://orcid.org/0000-0002-4508-9243)
- Panagiotis Garantziotis
- Armin Atzinger
- Andreas Wirsching
- Sara Chenguiti Fakhouri
- Moritz Ronicke (ORCID: https://orcid.org/0000-0001-8828-0980)
- Janina Auth (ORCID: https://orcid.org/0000-0002-5142-2620)
- Carlo Tur
- Andreas Ramming (ORCID: https://orcid.org/0000-0002-7003-501X)
- A. Zoli
- Aline Bözec (ORCID: https://orcid.org/0000-0001-8174-2118)
- Raymund E. Horch (ORCID: https://orcid.org/0000-0002-6561-2353)
- Aleix Rius Rigau (ORCID: https://orcid.org/0000-0002-0871-306X)
- Tobias Krickau (ORCID: https://orcid.org/0009-0002-2675-7610)
- Markus Eckstein (ORCID: https://orcid.org/0000-0001-5418-3349)
- Tim Filla (ORCID: https://orcid.org/0000-0001-5628-8398)
- Pooja Gupta (ORCID: https://orcid.org/0000-0002-3687-3853)
- Ziyuan Liu (ORCID: https://orcid.org/0000-0001-5564-7424)
- Meilin Xu
- Sebastian Böltz
- G Schett
- R Grieshaber-Bouyer
- Jörg HW Distler
- Melanie Hagen
- Christina Bergmann (ORCID: https://orcid.org/0000-0001-5257-9171)
- Yi-Nan Li (ORCID: https://orcid.org/0000-0001-8934-9361)
- Maria Gabriella Raimondo (ORCID: https://orcid.org/0000-0003-2020-6711)
- Manoj Kumar Selvaraju
- Fabian Müller (ORCID: https://orcid.org/0000-0001-5487-5839)
- Arif Ekici (ORCID: https://orcid.org/0000-0001-6099-7066)
- Paula Gehringer
- Andreas Mackensen (ORCID: https://orcid.org/0000-0002-0685-4483)
- Carola Berking (ORCID: https://orcid.org/0000-0003-0229-8931)
Institutions
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Agostino Gemelli University Polyclinic (IT)
- Universitätsklinikum Erlangen (DE)
- Düsseldorf University Hospital (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-23
- DOI
- https://doi.org/10.1038/s41467-026-72817-7
- Primary Topic
- Systemic Sclerosis and Related Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Friedrich-Alexander-Universität Erlangen-Nürnberg
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Forschungszentrum Jülich
- Heinrich-Heine-Universität Düsseldorf
- Staedtler Stiftung
- Deutsche Krebshilfe
- Siemens Healthineers
- German Network for Bioinformatics Infrastructure
- Leibniz-Gemeinschaft