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Publications

Journal Article Ahead of print

PubMed: 42177178 DOI: 10.1038/s41467-026-72817-7

Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells.

Nat Commun

Authors: Aleix Rius Rigau, Meilin Xu, Ziyuan Liu, Sara Chenguiti Fakhouri, Janina Auth, Panagiotis Garantziotis, Andrea Zoli, Manoj Kumar Selvaraju, Maria Gabriella Raimondo, Carlo Tur, Tim Filla, Paula Gehringer, Markus Eckstein, Fabian Müller, Armin Atzinger, Moritz Ronicke, Arif Ekici, Rafael Schmid, Andreas Wirsching, Melanie Hagen, Sebastian Böltz, Tobias Krickau, Raymund E Horch, Carola Berking, Ricardo Grieshaber-Bouyer, Andreas Ramming, Pooja Gupta, Aline Bozec, Andreas Mackensen, Jörg Hw Distler, Georg Schett, Yi-Nan Li, Christina Bergmann

Affiliations

  • Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany.
  • Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany.
  • Department of Rheumatology, Fondazione Policlinico Universitario A Gemelli, IRCSS, Catholic University of Sacred Heart, Rome, Italy.
  • Core Unit for Bioinformatics, Data integration and Analysis (CUBiDA), Medizinisches Zentrum für Informations- und Kommunikationstechnik (MIK), Universitätsklinikum, Erlangen, Germany.
  • Department of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Nuclear Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Pediatrics, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Department of Stem Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Spatial & Functional Screening Core Facility, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany.
  • Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.

Abstract

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.

MeSH

Skin, Cells, Sclerosis, Therapeutics, Tissues, Scleroderma, Systemic, Car-T Cell