ArticlemBio2016
Transcription Factor KLF2 in Dendritic Cells Downregulates Th2 Programming via the HIF-1α/Jagged2/Notch Axis.
Article in mBio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Vascular Notch-Related Protein Expression in a Rat Model of Central Venous Catheter-AssociatedPathogens (Basel, Switzerland) · 2026Article
- The Immunogenetic Landscape of Allergic Rhinitis: from Cellular Effectors to Gene Regulation and Targeted Therapies.International journal of biological sciences · 2026Review
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- The role of hypoxic microenvironment in autoimmune diseases.Frontiers in immunology · 2024Review
- Notch regulates Histoplasma capsulatum clearance in mouse lungs during innate and adaptive immune response phases in primary infection.Journal of leukocyte biology · 2022Article
- Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review.Frontiers in immunology · 2022Review
- Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back.Frontiers in immunology · 2022Review
- Notch signaling pathway in infectious diseases: role in the regulation of immune response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application.American journal of cancer research · 2021Review
- Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity.Journal for immunotherapy of cancer · 2019Article
- Notch Signaling Regulates Immune Responses in Atherosclerosis.Frontiers in immunology · 2019Review
- Hypoxia-inducible factor-1α regulation of myeloid cells.Journal of molecular medicine (Berlin, Germany) · 2018Review
- lncRNA LINC00673 induces proliferation, metastasis and epithelial-mesenchymal transition in thyroid carcinoma via Kruppel-like factor 2.International journal of oncology · 2018Article
- Gene expression analysis of Atlantic salmon gills reveals mucin 5 and interleukin 4/13 as key molecules during amoebic gill disease.Scientific reports · 2018Article
- Importance of EMT Factor ZEB1 in cDC1 "MutuDC Line" Mediated Induction of Th1 Immune Response.Frontiers in immunology · 2018Article
- T Cell-Restricted Notch Signaling Contributes to Pulmonary Th1 and Th2 Immunity duringJournal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
unlabelledThe adaptive immune response is tightly regulated by complex signals in dendritic cells (DCs). Although Th2 polarization is dictated by defined functional DC subsets, the molecular factors that govern the amplitude of these responses are not well understood. Krüppel-like factor 2 (KLF2) is a transcription factor that negatively regulates the activation of numerous immune cells in response to stimuli. Here, we demonstrate that suppression of KLF2 in conditioned DCs preferentially amplifies Th2 responses in two model systems, one of which is a prototypical intracellular pathogen and the other an allergen. This elevation in Th2 responses was dependent on contact-mediated Notch signaling in vitro and in vivo A deficiency of KLF2 increased the expression of Notch ligand Jagged2 via hypoxia-inducible factor 1α (HIF-1α), which led to Th2 amplification. Our results revealed a novel circuit in DCs for Th2 polarization that is governed by KLF2. IMPORTANCE: Dendritic cells are the key element that bridges innate and adaptive immunity. A complex and not-well-understood area in dendritic cell biology is the regulatory network that predetermines or moderates their function to shape the adaptive immune response. Our study for the first time demonstrates that KLF2, a transcription factor, conditions dendritic cells to regulate Th2 responses via a Jagged2/Notch axis. Downregulation of KLF2 expression in dendritic cells may provide a beneficial effect for treatment of diseases such as obesity or parasitic infections but may be deleterious in the case of invasion by intracellular pathogens. Strategies to tune KLF2 may be useful for future therapeutic approaches to particular diseases of mankind.
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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.