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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells
Aleix Rius Rigau1,2, Meilin Xu3,4, Ziyuan Liu1,2
1Department of Internal Medicine 3 - Rheumatology and Immunology, 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.
Insights
CD19-CAR T cell therapy shows promise for treating systemic sclerosis (SSc). This innovative treatment led to skin tissue regeneration and improved fibrotic disease markers in patients.
Area of Science:
- Immunology
- Dermatology
- Regenerative Medicine
Background:
- Systemic sclerosis (SSc) is an autoimmune disease causing problematic fibrotic tissue remodeling.
- Current therapies struggle to reverse SSc-induced fibrosis, necessitating novel regenerative strategies.
Purpose of the Study:
- To investigate the potential of CD19-CAR T cell therapy to induce tissue regeneration in patients with SSc.
- To analyze the effects of B cell depletion on skin structure, fibroblast populations, and vascular/epidermal function in SSc.
Main Methods:
- Analysis of skin biopsy samples from SSc patients treated with CD19-CAR T cell therapy (CASTLE study/named patient use).
- Histological examination for structural regeneration (e.g., skin papillae).
- Cyclic in situ hybridization and imaging mass cytometry to assess fibroblast, vascular, and epidermal cell changes.
Main Results:
- Demonstrated structural regeneration of SSc skin, including recovery of skin papillae.
- Observed a shift in fibroblast populations towards a physiological state (composition and function).
- Identified signs of vascular repair and altered epidermal cell function post-therapy.
Conclusions:
- CD19-CAR T cell therapy may induce significant skin tissue remodeling in SSc.
- B cell depletion via CD19-CAR T cell therapy shows potential for promoting tissue regeneration in fibrotic diseases like SSc.

