ArticleProceedings of the National Academy of Sciences of the United States of America2016
Arid5a exacerbates IFN-γ-mediated septic shock by stabilizing T-bet mRNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
- The RNA binding protein Arid5a is an activator of TNF signaling in rheumatoid arthritis.JCI insight · 2026Article
- A Quinoxaline Derivative as a New Therapeutic Agent for Sepsis through Suppression of TLR4 Signaling Pathways.Inflammation · 2025Article
- Growth of human regulatory CD4iScience · 2025Article
- DOCK2 protects against bacterial sepsis by constraining T helper 1 response.Frontiers in immunology · 2025Article
- Plasticity and Tumor Microenvironment in Pancreatic Cancer: Genetic, Metabolic, and Immune Perspectives.Cancers · 2024Review
- The RNA binding protein Arid5a drives IL-17-dependent autoantibody-induced glomerulonephritis.The Journal of experimental medicine · 2024Article
- Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation.The Journal of biological chemistry · 2024Article
- Bioinformatic Analysis of Roquin Family Reveals Their Potential Role in Immune System.International journal of molecular sciences · 2024Article
- Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.ImmunoTargets and therapy · 2024Article
- RNA Metabolism Governs Immune Function and Response.Advances in experimental medicine and biology · 2024Review
- RNA circuits and RNA-binding proteins in T cells.Trends in immunology · 2023Review
- The emerging role of Arid5a in cancer: A new target for tumors.Genes & diseases · 2023Review
- Arid5a Mediates an IL-17-Dependent Pathway That Drives Autoimmunity but Not Antifungal Host Defense.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Blockade of the Arid5a/IL-6/STAT3 axis underlies the anti-inflammatory effect of Rbpjl in acute pancreatitis.Cell & bioscience · 2022Article
- Orchestration of mesenchymal plasticity and immune evasivenessFrontiers in oncology · 2022Review
- Expression and Prognostic Value of ARID5A and its Correlation With Tumor-Infiltrating Immune Cells in Glioma.Frontiers in oncology · 2021Article
- Identification of a Five-Gene Prognostic Signature Related to B Cells Infiltration in Pancreatic Adenocarcinoma.International journal of general medicine · 2021Article
- Recent Advances in the Role of Arid5a in Immune Diseases and Cancer.Frontiers in immunology · 2021Review
- Differential modulation of Ahr and Arid5a: A promising therapeutic strategy for autoimmune encephalomyelitis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Historical overview of the interleukin-6 family cytokine.The Journal of experimental medicine · 2020Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we report that Arid5a-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxic shock and secrete lower levels of major proinflammatory cytokines, including IFN-γ, IL-6, and TNF-α, than WT mice in response to LPS. Arid5a deficiency resulted in decreased levels of IFN-γ under Th1 cell conditions, in which T-box expressed in T cells (T-bet) mRNA expression was inhibited. Arid5a bound to the conserved stem loop structure of the 3'UTR of T-bet and stabilized its mRNA. Arid5a-deficient mice were also resistant to Propionibacterium acnes-primed LPS injection, which is considered to be a T-cell-mediated IFN-γ dependent endotoxic shock mouse model. Thus, regulation of IFN-γ by Arid5a via the stabilization of T-bet mRNA in Th1 cells contributes to the development of septic shock in mice. In addition, our previous study suggests that Arid5a control the IL-6 level in vivo in response to LPS by stabilization of IL-6 mRNA. We also observed that neutralization of IFN-γ and IL-6 significantly recovered the mice from endotoxic shock. Taken together, we conclude that Arid5a regulates the augmentation of IL-6 and IFN-γ in response to LPS, which possibly works synergistically for amplification of various other cytokines that ultimately cause the development of septic shock in mice.
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