ArticleProceedings of the National Academy of Sciences of the United States of America2014
OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis.
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 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- OX40L Inhibition Suppresses KLH-driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof-of-Pharmacology for KY1005.Clinical pharmacology and therapeutics · 2022Trial
- OX40/OX40L modulation: A target for regulating T cells in cutaneous inflammatory disorders.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Review
- Immune checkpoint imbalance in ANCA-associated vasculitis: insights into disease activity and precision immunotherapy.Frontiers in medicine · 2026Review
- A novel bispecific antibody targeting OX40L and TNFα for the targeted treatment of rheumatoid arthritis.Antibody therapeutics · 2026Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Activation of NOD1 on tumor-associated macrophages augments CD8Science advances · 2024Article
- Sclerotic-Type Cutaneous Chronic Graft-Versus-Host Disease Exhibits Activation of T Helper 1 and OX40 Cytokines.The Journal of investigative dermatology · 2024Article
- OX40 (CD134) Expression on T Regulatory Cells Is Related to Serious Hypertensive Disorders in Pregnancy.Journal of cardiovascular development and disease · 2023Article
- MSM Supplementation Is Associated with Reduced Inflammation and Improved Innate Immune Response following In Vitro LPS-Stimulation in Humans after a Bout of Downhill Running.Muscles (Basel, Switzerland) · 2023Article
- Immune checkpoints in rheumatoid arthritis: progress and promise.Frontiers in immunology · 2023Review
- The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia.Molecular biology reports · 2021Article
- The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?International journal of molecular sciences · 2021Review
- Pharmacokinetic Engineering of OX40-Blocking Anticalin Proteins Using Monomeric Plasma Half-Life Extension Domains.Frontiers in pharmacology · 2021Article
- The OX40/OX40L Axis Regulates T Follicular Helper Cell Differentiation: Implications for Autoimmune Diseases.Frontiers in immunology · 2021Review
- Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection.International journal of molecular sciences · 2020Article
- Central Roles of OX40L-OX40 Interaction in the Induction and Progression of Human T Cell-Driven Acute Graft-versus-Host Disease.ImmunoHorizons · 2019Article
- Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia.Journal of immunology research · 2019Article
- A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.Journal of autoimmunity · 2018Review
- Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases.Nature reviews. Rheumatology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
An immune response is essential for protection against infection, but, in many individuals, aberrant responses against self tissues cause autoimmune diseases such as rheumatoid arthritis (RA). How to diminish the autoimmune response while not augmenting infectious risk is a challenge. Modern targeted therapies such as anti-TNF or anti-CD20 antibodies ameliorate disease, but at the cost of some increase in infectious risk. Approaches that might specifically reduce autoimmunity and tissue damage without infectious risk would be important. Here we describe that TNF superfamily member OX40 ligand (OX40L; CD252), which is expressed predominantly on antigen-presenting cells, and its receptor OX40 (on activated T cells), are restricted to the inflamed joint in arthritis in mice with collagen-induced arthritis and humans with RA. Blockade of this pathway in arthritic mice reduced inflammation and restored tissue integrity predominantly by inhibiting inflammatory cytokine production by OX40L-expressing macrophages. Furthermore, we identify a previously unknown role for OX40L in steady-state bone homeostasis. This work shows that more targeted approaches may augment the "therapeutic window" and increase the benefit/risk in RA, and possibly other autoimmune diseases, and are thus worth testing in humans.
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What OpenQuestion holds
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.