ArticleNature immunology2017
Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression.
Article in Nature immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
155 citing papers in PubMed, 1 synthesis or guideline pooled it, 275 citations in OpenAlex.
- Sarcoidosis as an Autoimmune Disease.Frontiers in immunology · 2019Pooled it
- Trial
- MMP12 induces fibrogenic macrophage differentiation to drive granuloma-associated cardiac fibrosis.American journal of respiratory and critical care medicine · 2026Article
- Sarcoidosis: A Clinical Trials Perspective.Pulmonary therapy · 2026Review
- Specific Biomarkers Involved in Sarcoidosis Diagnosis and Prognosis.International journal of molecular sciences · 2026Article
- Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Diagnosis and Management of Sarcoidosis-like Reaction in Adjuvant Immunotherapy: A Comprehensive Review and Clinical Implications.Biomedicines · 2026Review
- Diagnostic challenges in isolated cardiac sarcoidosis.ESC heart failure · 2026Review
- mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Unmasking Cardiac Sarcoidosis: Integrating Multimodal Imaging with Histochemical and Ultrastructural Analysis.International journal of molecular sciences · 2026Review
- Lymphocyte signal transduction defects in cutaneous sarcoidosis and implications for treatment.Frontiers in immunology · 2026Review
- Cardiac Sarcoidosis: Pathophysiology and Diagnostic-Therapeutic Processes.Reviews in cardiovascular medicine · 2026Review
- Single cell transcriptome signatures and cell-cell interactions associated with sarcoidosis in lung immune cell populations.Frontiers in immunology · 2026Article
- Contemporary management of sarcoidosis.Frontiers in medicine · 2026Review
- Immune-mediated cochleovestibular dysfunction: clinical spectrum from isolated inner-ear disorders to systemic autoimmune diseases and therapeutic strategies.Frontiers in immunology · 2026Review
- mTOR Signaling Pathway in Antiphospholipid Syndrome: Pathogenesis and Potential Therapeutic Targets.Drug design, development and therapy · 2026Review
- Diagnosis and treatment of sarcoidosis based on immunological etiology and mechanisms.Frontiers in medicine · 2026Review
- Pilot study identifying distinct circulating proteomic profiles associated with longitudinal CT-defined fibrotic and inflammatory sarcoidosis.Frontiers in immunology · 2026Article
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- Plasma Proteomic Profiling Reveals Distinct Signatures of Chest CT Phenotypes in Sarcoidosis.Research square · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo. TSC2-deficient macrophages formed mTORC1-dependent granulomatous structures in vitro and showed constitutive proliferation that was mediated by the neo-expression of cyclin-dependent kinase 4 (CDK4). Moreover, mTORC1 promoted metabolic reprogramming via CDK4 toward increased glycolysis while simultaneously inhibiting NF-κB signaling and apoptosis. Inhibition of mTORC1 induced apoptosis and completely resolved granulomas in myeloid TSC2-deficient mice. In human sarcoidosis patients, mTORC1 activation, macrophage proliferation and glycolysis were identified as hallmarks that correlated with clinical disease progression. Collectively, TSC2 maintains macrophage quiescence and prevents mTORC1-dependent granulomatous disease with clinical implications for sarcoidosis.
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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.