Targeting T cell plasticity in kidney and gut inflammation by pooled single-cell CRISPR screening.
Sci Immunol
; 9(96): eadd6774, 2024 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-38875317
ABSTRACT
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 (TH17) 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 TH17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (TH1) 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 TH17 to TH1 cell plasticity in the human kidney in the context of renal autoimmunity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Th17
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Análise de Célula Única
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha