ArticleProceedings of the National Academy of Sciences of the United States of America2014
A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8-induced IL-1.
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 50 papers.
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Who cites it
50 citing papers in PubMed, 65 citations in OpenAlex.
- Article
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- Article
- TNFSF15 alleviates myeloid-derived suppressor cell-mediated cancer immunosuppression in mice.Acta pharmacologica Sinica · 2026Article
- Bidirectional Communication Between the Innate and Adaptive Immune Systems.Annual review of immunology · 2025Review
- Review
- Linc00205/Mir-495-3p/Tnfsf15 Axis is Implicated in the Treatment Effect of Hyperbaric Oxygen Therapy on Patients with Post-Stroke Cognitive Impairment.Noro psikiyatri arsivi · 2025Article
- TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice.Cellular & molecular immunology · 2024Article
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- Leprosy: treatment, prevention, immune response and gene function.Frontiers in immunology · 2024Review
- Employing in silico investigations to determine the cross-kingdom approach forBeni-Suef University journal of basic and applied sciences · 2023Article
- Role of TNFSF15 variants in oral cancer development and clinicopathologic characteristics.Journal of cellular and molecular medicine · 2022Article
- Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.Genome biology · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis.Inflammatory bowel diseases · 2022Article
- Long-term association of pregnancy and maternal brain structure: the Rotterdam Study.European journal of epidemiology · 2022Article
- Utilising Network Pharmacology to Explore Underlying Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- TNFSF15 facilitates differentiation and polarization of macrophages toward M1 phenotype to inhibit tumor growth.Oncoimmunology · 2022Article
- Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response.The Journal of clinical investigation · 2021Article
- The E3 ubiquitin ligase RNF186 andProceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory diseases are characterized by dysregulated cytokine production. Altered functions for most risk loci, including the inflammatory bowel disease and leprosy-associated tumor necrosis factor ligand superfamily member 15 (TNFSF15) region, are unclear. Regulation of pattern-recognition-receptor (PRR)-induced signaling and cytokines is crucial for immune homeostasis; TNFSF15:death receptor 3 (DR3) contributions to PRR responses have not been described. We found that human macrophages expressed DR3 and that TNFSF15:DR3 interactions were critical for amplifying PRR-initiated MAPK/NF-κB/PI3K signaling and cytokine secretion in macrophages. Mechanisms mediating TNFSF15:DR3 contributions to PRR outcomes included TACE-induced TNFSF15 cleavage to soluble TNFSF15; soluble TNFSF15 then led to TRADD/FADD/MALT-1- and caspase-8-mediated autocrine IL-1 secretion. Notably, TNFSF15 treatment also induced cytokine secretion through a caspase-8-dependent pathway in intestinal myeloid cells. Importantly, rs6478108 A disease risk-carrier macrophages demonstrated increased TNFSF15 expression and PRR-induced signaling and cytokines. Taken together, TNFSF15:DR3 interactions amplify PRR-induced signaling and cytokines, and the rs6478108 TNFSF15 disease-risk polymorphism results in a gain of function.
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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.