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

2024-07-10 Wed
T cells plasticity kidney inflammation gut inflammation single-cell CRISPR autoimmune diseases
Targeting T Cell Plasticity to Treat Inflammation in the Kidney and Gut: A Study Using Pooled Single-cell CRISPR ScreeningBackground of the StudyThis paper, co-authored by Leon U.B. Enk and others, was published in the June 14, 2024, issue of “Science Immunology” under the title “Targeting T cell plasticity in kidney and gut inflammation by pooled single-cell CRISPR screening”. Current treatments for kidney and gut inflammations lack strategies to promote the conversion of T cell phenotypes to anti-inflammatory states. To address this issue, the study aims to use a pooled single-cell CRISPR screening method (iCROP-seq) to identify molecules affecting T cell polarization and plasticity in mouse models of nephritis and colitis. The goal is also to establish a method for identifying disease and tissue-specific therapeutic targets. The core of the study focuses on the plasticity of T helper 17 cells (Th17), which is crucial for developing T cell-regulating therapies.
Source of the StudyThis research was jointly conducted by scientists from the University Medical Center Hamburg-Eppendorf. The research team includes experts from various fields such as immunology, stem cell transplantation, medical statistics, and intelligent pharmacology.
MethodologyWorkflowIdentify the plasticity of Th17 cells in the kidneys of nephritis patients through single-cell T-cell receptor analysis and single-cell RNA velocity analysis.
Establish an in vivo pooled single-cell CRISPR screening method (iCROP-seq) applied to mouse models of nephritis and colitis.
Use CRISPR gene-targeting technology to knock out genes in Th17 cells and rank the genes based on the transcriptional disturbances caused.
Subjects and SamplesThe study includes 11 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN). In mouse models, the research involves mice with nephritis and colitis. Specially engineered CRISPR vectors were also utilized in the study.
Data Analysis AlgorithmsHigh-throughput single-cell sequencing technology was used in combination with CRISPR screening data to identify gene functions. Algorithms such as Euclidean distance and manifold enhancement of latent dimensions (MELD) were employed for the quantitative analysis of transcriptional disturbance results.
ResultsThe study found plasticity in Th17 cells in the kidneys of patients. iCROP-seq screening revealed molecular targeting strategies for Th17 cells in mouse models of nephritis and colitis.
Conclusions and ValueScientific ValueThe study demonstrates a novel in vivo tool for studying T cell plasticity, iCROP-seq, which can identify molecules related to T cell phenotype changes in animal models. This provides new insights and methods for developing T cell-regulating therapies.
Application ValueThe results of this study offer potential new targets for the treatment of autoimmune diseases such as nephritis and colitis. In the future, this may help clinicians more precisely modulate T cell responses for personalized patient treatment.
Research HighlightsA key finding is that iCROP-seq screening revealed critical genes affecting Th17 cell phenotypes, which may positively impact treatments for nephritis and colitis. The study’s methodology is innovative, combining high-throughput single-cell screening with CRISPR technology, thus proposing effective strategies for addressing treatment challenges in autoimmune diseases.
Additional Valuable InformationThe study further suggests the potential of applying iCROP-seq technology to other autoimmune disease models, such as psoriasis and multiple sclerosis, thereby expanding its application scope in future medical research. In terms of immunotherapy and immunomodulation, this study may open new doors for the identification of new immunological targets and the development of new drugs.