ArticleProceedings of the National Academy of Sciences of the United States of America2015
MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.Advanced biotechnology · 2026Review
- Mitophagy in inflammatory bowel disease: regulatory mechanisms and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Genome-wide association study of pulpal and apical diseases.Nature communications · 2025Article
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- Gene-environment interactions shape the host-microbial interface in inflammatory bowel disease.Nature immunology · 2025Review
- Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Genes Associated With POAG.Investigative ophthalmology & visual science · 2025Article
- The Myotubularin Related Proteins and the Untapped Interaction Potential of Their Disordered C-Terminal Regions.Proteins · 2025Article
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- Autophagy in inflammatory bowel disease: immunization, etiology, and therapeutic potential.Frontiers in immunology · 2025Review
- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population.International journal of general medicine · 2025Article
- Unraveling the role of autophagy regulation in Crohn's disease: from genetic mechanisms to potential therapeutics.Advanced biotechnology · 2024Review
- Autophagy in colitis-associated colon cancer: exploring its potential role in reducing initiation and preventing IBD-Related CAC development.Autophagy · 2024Review
- A potential therapeutic approach for ulcerative colitis: targeted regulation of mitochondrial dynamics and mitophagy through phytochemicals.Frontiers in immunology · 2024Review
- Review
- CLUH functions as a negative regulator of inflammation in human macrophages and determines ulcerative colitis pathogenesis.JCI insight · 2023Article
- The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease.Biochemical Society transactions · 2023Article
- Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy.Biomedicines · 2023Review
- Non-Synonymous Variants in Fat QTL Genes among High- and Low-Milk-Yielding Indigenous Breeds.Animals : an open access journal from MDPI · 2023Article
- Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease.Burns & trauma · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory bowel disease (IBD) is characterized by dysregulated host:microbial interactions and cytokine production. Host pattern recognition receptors (PRRs) are critical in regulating these interactions. Multiple genetic loci are associated with IBD, but altered functions for most, including in the rs713875 MTMR3/HORMAD2/LIF/OSM region, are unknown. We identified a previously undefined role for myotubularin-related protein 3 (MTMR3) in amplifying PRR-induced cytokine secretion in human macrophages and defined MTMR3-initiated mechanisms contributing to this amplification. MTMR3 decreased PRR-induced phosphatidylinositol 3-phosphate (PtdIns3P) and autophagy levels, thereby increasing PRR-induced caspase-1 activation, autocrine IL-1β secretion, NFκB signaling, and, ultimately, overall cytokine secretion. This MTMR3-mediated regulation required the N-terminal pleckstrin homology-GRAM domain and Cys413 within the phosphatase domain of MTMR3. In MTMR3-deficient macrophages, reducing the enhanced autophagy or restoring NFκB signaling rescued PRR-induced cytokines. Macrophages from rs713875 CC IBD risk carriers demonstrated increased MTMR3 expression and, in turn, decreased PRR-induced PtdIns3P and autophagy and increased PRR-induced caspase-1 activation, signaling, and cytokine secretion. Thus, the rs713875 IBD risk polymorphism increases MTMR3 expression, which modulates PRR-induced outcomes, ultimately leading to enhanced PRR-induced cytokines.
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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.