ArticleNature communications2022
In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- A unified network systems approach uncovers a core program underlying T follicular helper cell differentiation.Nature communications · 2026Article
- [Ubiquitination-mediated regulation of T cell homeostasis and autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function.bioRxiv : the preprint server for biology · 2026Article
- HIF-1αImmunity · 2026Article
- The MEK1/2-IRF4 axis fosters T follicular helper cell differentiationand antitumor humoral immune response.Journal of translational medicine · 2026Article
- In vivo CRISPR/Cas9 screens identify new regulators of B cell activation and plasma cell differentiation.The Journal of experimental medicine · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Metabolic reprogramming of immune cells in the battle against intracellular bacterial chronic infections: novel mechanisms and breakthroughs.Molecular biology reports · 2025Review
- Epstein-Barr virus-transformed B-cells from a hypoxia model of the germinal center requires external unsaturated fatty acids.PLoS pathogens · 2025Article
- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
- Targeting hypoxia-inducible factor 1α in chronic graft-versus-host disease to enhance graft-versus-leukemia responses: implications for nanotherapeutics.Frontiers in immunology · 2025Review
- High-throughput screening for optimizing adoptive T cell therapies.Experimental hematology & oncology · 2024Review
- Article
- Gα13 restricts nutrient driven proliferation in mucosal germinal centers.Nature immunology · 2024Article
- KLF2 determines the susceptibility of T cells to immunoregulatory NK cells.Research square · 2024Article
- Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.Science immunology · 2024Article
- Oligoclonal CD4Communications biology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction and are crucial for the generation of robust, long-lived antibody responses, but how the GC microenvironment affects Tfh cells is not well understood. Here we develop an in vivo T cell-intrinsic CRISPR-knockout screen to evaluate Tfh and Th1 cells in an acute viral infection model to identify regulators of Tfh cells in their physiological setting. Using a screen of druggable-targets, alongside genetic, transcriptomic and cellular analyses, we identify a function of HIF-1α in suppressing mTORC1-mediated and Myc-related pathways, and provide evidence that VHL-mediated degradation of HIF-1α is required for Tfh development; an expanded in vivo CRISPR screen reveals multiple components of these pathways that regulate Tfh versus Th1 cells, including signaling molecules, cell-cycle regulators, nutrient transporters, metabolic enzymes and autophagy mediators. Collectively, our data serve as a resource for studying Tfh versus Th1 decisions, and implicate the VHL-HIF-1α axis in fine-tuning Tfh generation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.