Targeting T cell plasticity in kidney and gut inflammation by pooled single-cell CRISPR screening.

Autor:	Enk LUB; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Hellmig M; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Riecken K; Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kilian C; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Datlinger P; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Jauch-Speer SL; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Neben T; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sultana Z; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sivayoganathan V; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Borchers A; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Paust HJ; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zhao Y; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Asada N; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Liu S; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Agalioti T; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Pelczar P; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Wiech T; Institute of Pathology, Division of Nephropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bock C; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.; Institute of Artificial Intelligence and Decision Support, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria., Huber TB; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Huber S; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bonn S; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Gagliani N; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Fehse B; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Stem Cell Transplantation, Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Panzer U; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Krebs CF; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2024 Jun 14; Vol. 9 (96), pp. eadd6774. Date of Electronic Publication: 2024 Jun 14.
DOI:	10.1126/sciimmunol.add6774
Abstrakt:	Pro-inflammatory CD4 + T cells are major drivers of autoimmune diseases, yet therapies modulating T cell phenotypes to promote an anti-inflammatory state are lacking. Here, we identify T helper 17 (T H 17) cell plasticity in the kidneys of patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis on the basis of single-cell (sc) T cell receptor analysis and scRNA velocity. To uncover molecules driving T cell polarization and plasticity, we established an in vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen and applied it to mouse models of glomerulonephritis and colitis. CRISPR-based gene targeting in T H 17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (T H 1) and regulatory T cells could be quantified. Furthermore, we show that iCROP-seq can facilitate the identification of therapeutic targets by efficient functional stratification of genes and pathways in a disease- and tissue-specific manner. These findings uncover T H 17 to T H 1 cell plasticity in the human kidney in the context of renal autoimmunity.
Databáze:	MEDLINE
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