ArticleNature communications2022
mTORC1 links pathology in experimental models of Still's disease and macrophage activation syndrome.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- CAR design equips diverse immune cells with unique antigen-specific activation identities.Molecular therapy. Oncology · 2026Article
- Type I Interferon Signature is Associated With Lung Disease, Drug-Associated Immune Reactions, and Genetic Variation in Interferon-Linked Pathways in Still Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Identification of a metabolic-immune crosstalk in Still's disease: monocyte/macrophage-derived immunometabolite itaconate dictates hepatic immunopathology via the CXCL10-CD8 T cell axis.Experimental & molecular medicine · 2026Article
- Still's Disease and Autoinflammation: Positioning an Inflammatory Syndrome on the Autoinflammation-Autoimmunity Spectrum.Current rheumatology reports · 2026Review
- TLR9 decreases FOXO3 expression to prevent excessive inflammation in macrophage activation syndrome.iScience · 2025Article
- Exploring the protective role of DDIT4/mTOR in podocyte integrity through macrophage polarization in diabetic kidney disease.Renal failure · 2025Article
- Macrophages lacking TSC2 have mTORC1-dependent increased GPNMB and ameliorate ventricular dysfunction/remodeling after ischemia-reperfusion.Scientific reports · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Integrated multi-omics characterization across clinically relevant subgroups of long COVID.National science review · 2025Article
- Article
- A case with systemic juvenile idiopathic arthritis treated with tofacitinib and rapamycin.Rheumatology (Oxford, England) · 2025Article
- T-ing up the storm: pathogenic cycling lymphocytes in the biology of macrophage activation syndrome.Pediatric rheumatology online journal · 2025Review
- Weal and woe of interleukin-18 in the T cell therapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Treating and triggering hyperinflammation: tackling hemophagocytic lymphohistiocytosis and HLH-like syndromes in the pediatric cell therapy and critical care setting.Frontiers in oncology · 2025Review
- The 'TNature reviews. Rheumatology · 2025Review
- New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.Expert review of clinical immunology · 2024Review
- New and future perspectives in familial Mediterranean fever and other autoinflammatory diseases.Archives of rheumatology · 2024Article
- Article
- Adult-Onset Still's Disease: An Atypical Presentation Refractory to Standard Treatment.Cureus · 2024Article
- Recent advances and evolving concepts in Still's disease.Nature reviews. Rheumatology · 2024Review
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Authors and funding
31 authors at 13 institutions in 4 countries.
Funding
Abstract
Still's disease is a severe inflammatory syndrome characterized by fever, skin rash and arthritis affecting children and adults. Patients with Still's disease may also develop macrophage activation syndrome, a potentially fatal complication of immune dysregulation resulting in cytokine storm. Here we show that mTORC1 (mechanistic target of rapamycin complex 1) underpins the pathology of Still's disease and macrophage activation syndrome. Single-cell RNA sequencing in a murine model of Still's disease shows preferential activation of mTORC1 in monocytes; both mTOR inhibition and monocyte depletion attenuate disease severity. Transcriptomic data from patients with Still's disease suggest decreased expression of the mTORC1 inhibitors TSC1/TSC2 and an mTORC1 gene signature that strongly correlates with disease activity and treatment response. Unrestricted activation of mTORC1 by Tsc2 deletion in mice is sufficient to trigger a Still's disease-like syndrome, including both inflammatory arthritis and macrophage activation syndrome with hemophagocytosis, a cellular manifestation that is reproduced in human monocytes by CRISPR/Cas-mediated deletion of TSC2. Consistent with this observation, hemophagocytic histiocytes from patients with macrophage activation syndrome display prominent mTORC1 activity. Our study suggests a mechanistic link of mTORC1 to inflammation that connects the pathogenesis of Still's disease and macrophage activation syndrome.
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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.