ArticleThe Journal of experimental medicine2016
--LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
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- Soluble CD95L triggers Caspase-10-driven reactive oxygen species production in neutrophils and aggravates anti-neutrophil cytoplasmic antibody-vasculitis.Nature communications · 2026Article
- Lysine-11 ubiquitination drives type-I/III interferon induction by cGAS-STING and Toll-like receptors 3 and 4.Nature cell biology · 2026Article
- Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation.Cell research · 2025Article
- Review
- Innate Immune Sensors and Cell Death-Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin.Viruses · 2025Review
- Interplay between Pro-inflammatory Mediators and Oxidative Stressinvolved Recurrent Chronic Heart Failure in Elderly Patients with Coronary Stents.Current medicinal chemistry · 2025Article
- For Better or Worse: The Impact of Necrotic Cell Death Modalities.Advances in experimental medicine and biology · 2025Review
- Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications.Cell death & disease · 2024Review
- LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.Cell death and differentiation · 2024Article
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 2024Article
- Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.Nature immunology · 2024Article
- Caspase cleavage of RIPK3 after AspCell death and differentiation · 2024Article
- Mind bomb 2 limits inflammatory dermatitis inPNAS nexus · 2024Article
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- LUBAC is required for RIG-I sensing of RNA viruses.Cell death and differentiation · 2024Article
- HOIL1 Regulates Group 3 Innate Lymphoid Cells in the Colon and Protects against Systemic Dissemination, Colonic Ulceration, and Lethality from Citrobacter rodentium Infection.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- Toll-Like Receptor 3 mRNA Expression of Peripheral Blood Mononuclear Cells Identifies Kidney Recipients with Potential for Improved Graft Performance.Annals of transplantation · 2023Article
- Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair.Science advances · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain-interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1-interacting protein (HOIP), is a critical regulator of inflammation and immunity. This is highlighted by the fact that patients with perturbed linear ubiquitination caused by mutations in the Hoip or Hoil-1 genes, resulting in knockouts of these proteins, may simultaneously suffer from immunodeficiency and autoinflammation. TLR3 plays a crucial, albeit controversial, role in viral infection and tissue damage. We identify a pivotal role of LUBAC in TLR3 signaling and discover a functional interaction between LUBAC components and TLR3 as crucial for immunity to influenza A virus infection. On the biochemical level, we identify LUBAC components as interacting with the TLR3-signaling complex (SC), thereby enabling TLR3-mediated gene activation. Absence of LUBAC components increases formation of a previously unrecognized TLR3-induced death-inducing SC, leading to enhanced cell death. Intriguingly, excessive TLR3-mediated cell death, induced by double-stranded RNA present in the skin of SHARPIN-deficient chronic proliferative dermatitis mice (cpdm), is a major contributor to their autoinflammatory skin phenotype, as genetic coablation of Tlr3 substantially ameliorated cpdm dermatitis. Thus, LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation.
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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.