ArticleProceedings of the National Academy of Sciences of the United States of America2014
T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
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- Metabolic stress and age drive inflammation and cognitive decline in mice and humans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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- Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.Signal transduction and targeted therapy · 2023Article
- Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).International immunology · 2023Review
- Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease.Veterinary pathology · 2022Article
- Secreted osteopontin from CD4Cell reports · 2021Article
- Serum MMP3 Correlated With IL1β Messenger RNA Expressions of Peripheral Blood Mononuclear Cells in Patients With Relapsing Polychondritis With Respiratory Involvement.ACR open rheumatology · 2021Article
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- Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19.Frontiers in immunology · 2021Review
- AAV-Mediated Combination Gene Therapy for Neuropathic Pain: GAD65, GDNF, and IL-10.Molecular therapy. Methods & clinical development · 2020Article
- Myeloid Cell-Intrinsic IRF5 Promotes T Cell Responses through Multiple Distinct Checkpoints In Vivo, andJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling.Yonsei medical journal · 2020Article
- T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation.Cell reports · 2020Article
- TLR4 mediates alveolar bone resorption in experimental peri-implantitis through regulation of CD45Journal of periodontology · 2020Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Endotoxemia is caused by excessive inflammation, but the immune system has various mechanisms to avoid collateral organ damage in endotoxemia. A handful of reports have shown that innate immune responses are suppressed by the adaptive immune system. However, the molecular mechanism by which adaptive immune cells suppress innate inflammatory responses is not clear. Here, we report that T cells are shown to interact with macrophages at the early stage of enodotoxemia and to prolong survival of mice through controlling TNF and IL-10 levels by macrophage CD40 stimulation. The cross-talk between CD40 and toll-like receptor (TLR4) signaling first mediates IL-1 receptor-associated kinase 1 (IRAK1) nuclear translocation and its binding to the IL-10 gene promoter in macrophages, without interfering with the NFκB pathway. IL-10 is then detected by macrophages in an autocrine fashion to destabilize Tnfa mRNA. To induce IRAK1-mediated IL-10 expression, signals from both CD40 and TLR4 are essential. CD40 signaling induces IRAK1 sumoylation in the presence of TNF receptor-associated factor 2 (TRAF2) and intracellular isoform of osteopontin (iOPN) whereas TLR4 signaling provides IFN regulatory factor 5 (IRF5) as a chaperone for sumoylated IRAK1 nuclear translocation. Interaction of T cells with macrophages was observed in the spleen in vivo after endotoxemia induction with LPS injection. Our study demonstrates a mechanistic basis for the immunosuppressive role of macrophage CD40 in LPS endotoxemia.
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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.