Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells
Abstract
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.
Article Details
Authors (33)
Aleix Rius Rigau
Meilin Xu
Ziyuan Liu
Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry
Sara Chenguiti Fakhouri
Janina Auth
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Panagiotis Garantziotis
Andrea Zoli
Manoj Kumar Selvaraju
Maria Gabriella Raimondo
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Carlo Tur
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Tim Filla
Paula Gehringer
Markus Eckstein
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Fabian Müller
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Armin Atzinger
Moritz Ronicke
Arif Ekici
Rafael Schmid
Andreas Wirsching
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Melanie Hagen
Sebastian Böltz
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Tobias Krickau
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Raymund E. Horch
Carola Berking
Ricardo Grieshaber-Bouyer
Andreas Ramming
Pooja Gupta
York Structural Biology Laboratory, Department of Chemistry, University of York
Aline Bozec
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany
Andreas Mackensen
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Jörg HW Distler
Georg Schett
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Yi-Nan Li
Christina Bergmann
Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany