ArticleJCI insight2020
The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
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- Identification of miRNA Biomarkers Associated With Staphylococcal Musculoskeletal Infections.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Gene Expression Dysregulation in Whole Blood of Patients withInternational journal of molecular sciences · 2024Article
- E3 ubiquitin ligase RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα.Cell communication and signaling : CCS · 2024Article
- Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.Nature immunology · 2024Article
- Crosstalk of ubiquitin system and non-coding RNA in fibrosis.International journal of biological sciences · 2024Review
- IL-3: key orchestrator of inflammation.Frontiers in immunology · 2024Review
- Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age-associated mRNAs and long noncoding RNAs.Aging cell · 2023Article
- Comprehensive analysis of CPSF4-related alternative splice genes in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity.Military Medical Research · 2022Review
- N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer.Cancer cell international · 2022Article
- Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders.Nature communications · 2022Article
- MARCH3 negatively regulates IL-3-triggered inflammatory response by mediating K48-linked polyubiquitination and degradation of IL-3Rα.Signal transduction and targeted therapy · 2022Article
- Novel CD123 polyaptamer hydrogel edited by Cas9/sgRNA for AML-targeted therapy.Drug delivery · 2021Article
- Pharmacogenetic studies of long-acting beta agonist and inhaled corticosteroid responsiveness in randomised controlled trials of individuals of African descent with asthma.The Lancet. Child & adolescent health · 2021Article
- Adipocyte-specific deletion of HuR induces spontaneous cardiac hypertrophy and fibrosis.American journal of physiology. Heart and circulatory physiology · 2021Article
- LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications.Frontiers in immunology · 2021Article
- The β3/5 Integrin-MMP9 Axis Regulates Pulmonary Inflammatory Response and Endothelial Leakage in Acute Lung Injury.Journal of inflammation research · 2021Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Interleukin-3 (IL-3) receptor α (IL-3Rα) is the α subunit of the ligand-specific IL-3R and initiates intracellular signaling in response to IL-3. IL-3 amplifies proinflammatory signaling and cytokine storm in murine sepsis models. Here we found that RNFT2 (RING finger transmembrane-domain containing protein 2, also TMEM118), a previously uncharacterized RING finger ubiquitin E3 ligase, negatively regulated IL-3-dependent cellular responses through IL-3Rα ubiquitination and degradation in the proteasome. In vitro, IL-3 stimulation promoted IL-3Rα proteasomal degradation dependent on RNFT2, and we identified IL-3Rα lysine 357 as a ubiquitin acceptor site. We determined that LPS priming reduces RNFT2 abundance, extends IL-3Rα half-life, and sensitizes cells to the effects of IL-3, acting synergistically to increase proinflammatory signaling. In vivo, IL-3 synergized with LPS to exacerbate lung inflammation in LPS and Pseudomonas aeruginosa-challenged mice; conversely, IL-3 neutralization reduced LPS-induced lung injury. Further, RNFT2 overexpression reduced lung inflammation and injury, whereas Rnft2 knockdown exacerbated inflammatory responses in LPS-induced murine lung injury. Last, we examined RNFT2 and IL-3Rα in human lung explants from patients with cystic fibrosis and also showed that IL-3 is elevated in mechanically ventilated critically ill humans at risk for acute respiratory distress syndrome. These results identify RNFT2 as a negative regulator of IL-3Rα and show a potential role for the RNFT2/IL-3Rα/IL-3 axis in regulating innate immune responses in the lung.
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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 Socratic graph.