ArticleCell cycle (Georgetown, Tex.)2009
Treg versus Th17 lymphocyte lineages are cross-regulated by LIF versus IL-6.
Article in Cell cycle (Georgetown, Tex.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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
73 citing papers in PubMed, 133 citations in OpenAlex.
- Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes.European journal of immunology · 2016Trial
- Targeting androgen receptor as a novel radiosensitizing therapy to improve long-term survival and anti-tumor immunity in glioblastoma via TGF-β/Smad3 Axis reprogramming.Cell death discovery · 2026Article
- Investigating the Role of Anti-Leukemia Inhibitory Factor Antibody on Cytokine Profile in a Mouse Model of Breast Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
- Early Postreperfusion Proteomics Reveal Divergent Inflammatory Responses in Kidney Transplantation With Implications on Outcomes.Transplantation · 2026Article
- Targeting Androgen Receptor as a Novel Radiosensitizing Therapy to Improve Long-Term Survival and Anti-tumor Immunity in Glioblastoma via TGF-β/Smad3 Axis Reprogramming.Research square · 2026Article
- Unveiling natural anti-inflammatory compounds for sinusitis treatments by modulating FOXP3, C5aR1, and LIF.Frontiers in immunology · 2026Review
- Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus.BMC genomics · 2025Article
- An optimised faecal microRNA sequencing pipeline reveals fibrosis in Trichuris muris infection.Nature communications · 2025Article
- Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.Journal of inflammation research · 2025Review
- Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases.Life (Basel, Switzerland) · 2024Review
- A mechanistic PK/PD model of AZD0171 (anti-LIF) to support Phase II dose selection.CPT: pharmacometrics & systems pharmacology · 2024Article
- Suppressor of Cytokine Signaling Proteins 3 and 5 Potentially Delineate Polarization of Th cells in Chronic Rhinosinusitis.The Yale journal of biology and medicine · 2024Article
- Review
- The effect of the anti-leukemia inhibitory factor on the immune system in the Balb/c mice bearing breast cancer induced with 4T1 cells.European journal of medical research · 2023Article
- Leukemia inhibitory factor, a double-edged sword with therapeutic implications in human diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- The dysregulation of leukemia inhibitory factor and its implications for endometriosis pathophysiology.Frontiers in immunology · 2023Article
- 3DFAACTS-SNP: using regulatory T cell-specific epigenomics data to uncover candidate mechanisms of type 1 diabetes (T1D) risk.Epigenetics & chromatin · 2022Article
- The emerging role of leukemia inhibitory factor in cancer and therapy.Pharmacology & therapeutics · 2021Review
- Leukemia Inhibitory Factor: A Potential Biomarker and Therapeutic Target in Pancreatic Cancer.Archivum immunologiae et therapiae experimentalis · 2021Review
- Human Tendon Stem/Progenitor Cell Features and Functionality Are Highly Influenced byFrontiers in bioengineering and biotechnology · 2021Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Within the immune system there is an exquisite ability to discriminate between "self" and "non-self" that is orchestrated by T lymphocytes. Discriminatory pathways guide differentiation of these lymphocytes into either regulatory (Treg) or effector (Teff) T cells, influenced by cues from the naïve T cell's immediate micro-environment as it responds to cognate antigen. Reciprocal pathways may lead to commitment of naïve T cells into either the protective tolerance-promoting Treg, or to the pro-inflammatory Th17 effector phenotype. Primary activation of CD4(+) lymphocytes stimulates their release of leukemia inhibitory factor (LIF), and Treg continue to release LIF in response to antigen, implying a role for LIF in tolerance. In contrast, interleukin- 6 (IL-6), although very closely related to LIF, promotes maturation of Th17 cells. Here we show that LIF and IL-6 behave as polar opposites in promoting commitment to the Treg and Th17 lineages. Unlike IL6, LIF supported expression of Foxp3, the Treg lineage transcription factor, and LIF opposed IL6 by suppressing IL-6-induced IL-17A protein release. In striking contrast, we found that IL6 effectively inhibited LIF signalling, repressing transcription of the LIF receptor gp190, and strongly inducing axotrophin/MARCH-7, a novel E3 ubitquitin ligase that we discovered to be active in degradation of gp190 protein. In vivo, anti-LIF treatment reduced donor-specific Treg in recipients of foreign spleen cells. Conversely, a single dose of biodegradable LIF nanoparticles, targeted to CD4, successfully manipulated the LIF/IL6 axis towards development of donor-specific Foxp3(+) Treg. The implications for therapy are profound, harnessing endogenous immune regulation by paracrine delivery of LIF to CD4(+) cells in vivo.
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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.