Selective CAR T cell–mediated B cell depletion suppresses IFN signature in SLE

Wilhelm A, Chambers D, Müller F, Bozec A, Grieshaber Bouyer R, Winkler T, Mougiakakos D, Mackensen A, Schett G, Krönke G (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

JCI Insight American Society for Clinical Investigation

Book Volume: 9

Article Number: e179433

Journal Issue: 12

DOI: 10.1172/jci.insight.179433

Abstract

Applying advanced molecular profiling together with highly specific targeted therapies offers the possibility to better dissect the mechanisms underlying immune-mediated inflammatory diseases such as systemic lupus erythematosus (SLE) in humans. Here we apply a combination of single-cell RNA-Seq and T/B cell repertoire analysis to perform an in-depth characterization of molecular changes in the immune-signature upon CD19 CAR T cell–mediated depletion of B cells in patients with SLE. The resulting data sets not only confirm a selective CAR T cell–mediated reset of the B cell response but simultaneously reveal consequent changes in the transcriptional signature of monocyte and T cell subsets that respond with a profound reduction in type I IFN signaling. Our current data, thus, provide evidence for a causal relationship between the B cell response and the increased IFN signature observed in SLE and additionally demonstrate the usefulness of combining targeted therapies and analytic approaches to decipher molecular mechanisms of immune-mediated inflammatory diseases in humans.

Authors with CRIS profile

Artur Wilhelm Department of Medicine 3 – Rheumatology and Immunology David Chambers Department of Medicine 3 – Rheumatology and Immunology Fabian Müller Department of Medicine 5 – Haematology and Oncology Aline Bozec Professur für Experimentelle Immuntherapie Ricardo Grieshaber Bouyer Professur für Klinische Systemimmunologie Thomas Winkler Professur für Genetik Andreas Mackensen Lehrstuhl für Innere Medizin V Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Otto-von-Guericke-Universität Magdeburg DE Germany (DE)

How to cite

APA:

Wilhelm, A., Chambers, D., Müller, F., Bozec, A., Grieshaber Bouyer, R., Winkler, T.,... Krönke, G. (2024). Selective CAR T cell–mediated B cell depletion suppresses IFN signature in SLE. JCI Insight, 9(12). https://doi.org/10.1172/jci.insight.179433

MLA:

Wilhelm, Artur, et al. "Selective CAR T cell–mediated B cell depletion suppresses IFN signature in SLE." JCI Insight 9.12 (2024).

BibTeX: Download