CRISPR screens for functional interrogation of immunity

Shi, Hao; Doench, John G.; Chi, Hongbo

doi:10.1038/s41577-022-00802-4

Cited by 21 publications

(19 citation statements)

References 192 publications

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“…Further, CRISPR-Cas9-based genetic screening can be applied to interrogate the causative effects of lipid metabolism and DC biology on a large scale. 114 The integrative use of combinatorial or complementary approaches (e.g., pharmacological inhibition, genetic perturbation, and systems biology approaches) will uncover key lipid metabolism-related mechanisms that regulate DC function in diverse contexts and facilitate the development of new therapeutic strategies.…”

Section: Lipid Me Tabolis M and D C Fun C Ti On In The Tmementioning

confidence: 99%

“…Additionally, applications of systems‐level approaches such as metabolomics, proteomics, ATAC‐seq, single‐cell RNA‐seq, and other single cell‐based approaches (e.g., SCENITH and MetFlow 112,113 ) will help us to dissect the mechanisms by which lipid metabolism orchestrates DC biology. Further, CRISPR–Cas9‐based genetic screening can be applied to interrogate the causative effects of lipid metabolism and DC biology on a large scale 114 . The integrative use of combinatorial or complementary approaches (e.g., pharmacological inhibition, genetic perturbation, and systems biology approaches) will uncover key lipid metabolism‐related mechanisms that regulate DC function in diverse contexts and facilitate the development of new therapeutic strategies.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

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Lipid metabolism in dendritic cell biology

You

Chi

2023

Immunological Reviews

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SummaryDendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity. Immune signals and microenvironmental cues shape the function of DC subsets in different contexts, which is associated with reprogramming of cellular metabolic pathways. In addition to integrating these extracellular cues to meet bioenergetic and biosynthetic demands, cellular metabolism interplays with immune signaling to shape DC‐dependent immune responses. Emerging evidence indicates that lipid metabolism serves as a key regulator of DC responses. Here, we summarize the roles of fatty acid and cholesterol metabolism, as well as selective metabolites, in orchestrating the functions of DCs. Specifically, we highlight how different lipid metabolic programs, including de novo fatty acid synthesis, fatty acid β oxidation, lipid storage, and cholesterol efflux, influence DC function in different contexts. Further, we discuss how dysregulation of lipid metabolism shapes DC intracellular signaling and contributes to the impaired DC function in the tumor microenvironment. Finally, we conclude with a discussion on key future directions for the regulation of DC biology by lipid metabolism. Insights into the connections between lipid metabolism and DC functional specialization may facilitate the development of new therapeutic strategies for human diseases.

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Section: Lipid Me Tabolis M and D C Fun C Ti On In The Tmementioning

confidence: 99%

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Lipid metabolism in dendritic cell biology

You

Chi

2023

Immunological Reviews

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“…Many researchers have applied CRISPR screening in immune cells to investigate questions in tumor immunology (reviewed elsewhere) ( Li & Fei, 2020 ; Shi et al, 2022 ), but very few studies are linked to cardiovascular diseases. Inflammation plays a prominent role in the development of cardiovascular diseases such as atherosclerosis which involves inflammation-induced endothelial dysfunction and interplay between blood vessel cells and inflammation-related immune cells (e.g., monocytes and macrophages) ( Henein et al, 2022 ).…”

Section: Crispr Screening In Cardiovascular Researchmentioning

confidence: 99%

CRISPR screening in cardiovascular research

Shan

Teng

2023

Front. Cell Dev. Biol.

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The recent advent and widespread application of CRISPR-based genome editing tools have revolutionized biomedical research and beyond. Taking advantage of high perturbation efficiency and scalability, CRISPR screening has been regarded as one of the most powerful technologies in functional genomics which allows investigation of different genetic subjects at a large scale in parallel. Significant progress has been made using various CRISPR screening tools especially in cancer research, however, fewer attempts and less success are reported in other contexts. In this mini-review, we discuss how CRISPR screening has been implemented in studies on cardiovascular research and related metabolic disorders, highlight the scientific progress utilizing CRISPR screening, and further envision how to fully unleash the power of this technique to expedite scientific discoveries in these fields.

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“…and Shigella [26] infection, macrophage regulation of phagocytosis [27] and T-cell activation via IFNγ-inducible MHCII [28]. Many T-cell and tumor immunology CRISPR screens provided major breakthroughs toward the understanding of the disease mechanisms [29].…”

Section: Transcriptomics and Genomicsmentioning

confidence: 99%

“…Major advancements in functional genomics, applied widely to immunology, came with the development of CRISPR screens, which have been applied to innate immunity in the studies of TLR4 [23], NLRP3 inflammasome [24], host factors modulating Salmonella [25], and Shigella [26] infection, macrophage regulation of phagocytosis [27] and T‐cell activation via IFNγ‐inducible MHCII [28]. Many T‐cell and tumor immunology CRISPR screens provided major breakthroughs toward the understanding of the disease mechanisms [29].…”

Section: Multiomics In Innate Immunitymentioning

confidence: 99%

Omics and systems view of innate immune pathways

2023

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Multiomics approaches to studying systems biology are very powerful techniques that can elucidate changes in the genomic, transcriptomic, proteomic, and metabolomic levels within a cell type in response to an infection. These approaches are valuable for understanding the mechanisms behind disease pathogenesis and how the immune system responds to being challenged. With the emergence of the COVID‐19 pandemic, the importance and utility of these tools have become evident in garnering a better understanding of the systems biology within the innate and adaptive immune response and for developing treatments and preventative measures for new and emerging pathogens that pose a threat to human health. In this review, we focus on state‐of‐the‐art omics technologies within the scope of innate immunity.

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CRISPR screens for functional interrogation of immunity

Cited by 21 publications

References 192 publications

Lipid metabolism in dendritic cell biology

Lipid metabolism in dendritic cell biology

CRISPR screening in cardiovascular research

Omics and systems view of innate immune pathways

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