ArticleThe Journal of clinical investigation2010
Mammalian target of rapamycin activation underlies HSC defects in autoimmune disease and inflammation in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers.
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
68 citing papers in PubMed, 100 citations in OpenAlex.
- Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy.Cell reports. Medicine · 2023Trial
- A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.Experimental gerontology · 2018Trial
- Exploiting cellular senescence in hematologic malignancies.Translational oncology · 2026Review
- Inflammation starves antitumour immunity.Nature cell biology · 2026Article
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- Article
- CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment.bioRxiv : the preprint server for biology · 2023Article
- Article
- The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies.Bone research · 2023Review
- Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway.EMBO reports · 2023Article
- BATF sustains homeostasis and functionality of bone marrow Treg cells to preserve homeostatic regulation of hematopoiesis and development of B cells.Frontiers in immunology · 2023Article
- Selective ablation of thymic and peripheral Foxp3Frontiers in immunology · 2023Article
- Case report: Severe asymptomatic hypertriglyceridemia associated with long-term low-dose rapamycin administration in a healthy middle-aged Labrador retriever.Frontiers in veterinary science · 2023Article
- Regulation of eIF4E guides a unique translational program to control erythroid maturation.Science advances · 2022Article
- Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system.Nature communications · 2022Article
- Hematopoietic Stem Cells and Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- A complex proinflammatory cascade mediates the activation of HSCs upon LPS exposure in vivo.Blood advances · 2022Article
- Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization.Aging cell · 2022Review
- Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis.Acta pharmaceutica Sinica. B · 2022Article
- Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) is a signaling molecule that senses environmental cues, such as nutrient status and oxygen supply, to regulate cell growth, proliferation, and other functions. Unchecked, sustained mTOR activity results in defects in HSC function. Inflammatory conditions, such as autoimmune disease, are often associated with defective hematopoiesis. Here, we investigated whether hyperactivation of mTOR in HSCs contributes to hematopoietic defects in autoimmunity and inflammation. We found that in mice deficient in Foxp3 (scurfy mice), a model of autoimmunity, the development of autoimmune disease correlated with progressive bone marrow loss and impaired regenerative capacity of HSCs in competitive bone marrow transplantation. Similarly, LPS-mediated inflammation in C57BL/6 mice led to massive bone marrow cell death and impaired HSC function. Importantly, treatment with rapamycin in both models corrected bone marrow hypocellularity and partially restored hematopoietic activity. In cultured mouse bone marrow cells, treatment with either of the inflammatory cytokines IL-6 or TNF-α was sufficient to activate mTOR, while preventing mTOR activation in vivo required simultaneous inhibition of CCL2, IL-6, and TNF-α. These data strongly suggest that mTOR activation in HSCs by inflammatory cytokines underlies defective hematopoiesis in autoimmune disease and inflammation.
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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.