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

• DOI: 10.1126/sciimmunol.add6774
• Publication Date: 2024-06-14T18:01:11Z
• Authors: Leon U. B. Enk; Malte Hellmig; Kristoffer Riecken; Christoph Kilian; Paul Datlinger; Saskia L. Jauch-S...; Tobias Neben; Zeba Sultana; Varshi Sivayogana...; Alina Borchers; Hans-Joachim Paust; Yu Zhao; Nariaki Asada; Shuya Liu; Theodora Agalioti; Penelope Pelczar; Thorsten Wiech; Christoph Bock; Tobias B. Huber; Samuel Huber; Stefan Bonn; Nicola Gagliani; Boris Fehse; Ulf Panzer; Christian F. Krebs
• Keywords: Inflammation; Male; 0303 health sciences; Cell Plasticity; Kidney; Colitis; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Glomerulonephritis; Animals; Humans; Th17 Cells; Female; Clustered Regularly Interspaced Short Palindromic Repeats; Single-Cell Analysis; CRISPR-Cas Systems

Pro-inflammatory CD4 + T cells are major drivers of autoimmune diseases, yet therapies modulating cell phenotypes to promote an anti-inflammatory state lacking. Here, we identify helper 17 (T H 17) plasticity in the kidneys patients with antineutrophil cytoplasmic antibody–associated glomerulonephritis on basis single-cell (sc) receptor analysis and scRNA velocity. To uncover molecules driving polarization plasticity, established vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen applied it mouse models colitis. CRISPR-based gene targeting could be ranked according resulting transcriptional perturbations, biases into 1 1) regulatory quantified. Furthermore, show that iCROP-seq can facilitate identification therapeutic targets by efficient functional stratification genes pathways a disease- tissue-specific manner. These findings human kidney context renal autoimmunity.