ArticleThe Journal of clinical investigation2020
Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Monitoring Neurocognitive Functioning After Pediatric Cellular Therapy or Hematopoietic Cell Transplant: Guidelines From the COG Neurocognition in Cellular Therapies Task Force.Transplantation and cellular therapy · 2022Guideline
- Dynamic Metabolic Profiling and Diagnostic Biomarkers of Acute Graft-Versus-Host Disease Based on Metabolomics.Biomedical chromatography : BMC · 2026Article
- Successful use of ruxolitinib in steroid-refractory chronic GvHD affecting central nervous system: a case report.Annals of hematology · 2026Article
- A transcriptomic microglia taxonomy across mouse and human pathologies.Nature immunology · 2026Article
- Allogeneic MHC-mismatched microglia-like cell replacement as a therapeutic approach for multiple sclerosis.Journal of neuroinflammation · 2026Article
- Neurological graft-versus-host disease with MOG antibody positivity after allogeneic stem cell transplantation: a case report.Frontiers in immunology · 2026Article
- AIstain: Enhancing microglial phagocytosis analysis through deep learning.Cell reports methods · 2025Article
- AhR activation mitigates graft-versus-host disease of the central nervous system by reducing microglial NF-κB signaling.Blood advances · 2025Article
- Understanding TAK1 deficiency in microglia: Dual mechanisms for photoreceptor protection in a mouse model of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advantages and challenges of using allogeneic vs. autologous sources for neuronal cell replacement in Parkinson's disease: Insights from non-human primate studies.Brain research bulletin · 2025Review
- CNS manifestations in acute and chronic graft-versus-host disease.Brain : a journal of neurology · 2025Article
- Review
- Cell-type-specific regulators landscape and regulatory mechanisms underlying pyroptosis in uterine corpus endometrial carcinoma.Journal of Cancer · 2025Article
- Allogeneic Mouse Models of Graft-Versus-Host Disease.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Targeting TAK1 in microglia to treat CAR T cell neurotoxicity.Nature cancer · 2024Article
- Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome.Nature cancer · 2024Article
- The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.Investigative ophthalmology & visual science · 2024Article
- Thrombin receptor activating peptide-6 decreases acute graft-versus-host disease through activating GPR15.Leukemia · 2024Article
- CSF-1R inhibitor PLX3397 attenuates peripheral and brain chronic GVHD and improves functional outcomes in mice.Journal of neuroinflammation · 2023Article
- Acute graft-versus-host disease.Nature reviews. Disease primers · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 7 countries.
Funding
Abstract
Acute graft-versus-host disease (GVHD) can affect the central nervous system (CNS). The role of microglia in CNS-GVHD remains undefined. In agreement with microglia activation, we found that profound morphological changes and MHC-II and CD80 upregulation occurred upon GVHD induction. RNA sequencing-based analysis of purified microglia obtained from mice with CNS-GVHD revealed TNF upregulation. Selective TNF gene deletion in microglia of Cx3cr1creER Tnffl/- mice reduced MHC-II expression and decreased CNS T cell infiltrates and VCAM-1+ endothelial cells. GVHD increased microglia TGF-β-activated kinase-1 (TAK1) activation and NF-κB/p38 MAPK signaling. Selective Tak1 deletion in microglia using Cx3cr1creER Tak1fl/fl mice resulted in reduced TNF production and microglial MHC-II and improved neurocognitive activity. Pharmacological TAK1 inhibition reduced TNF production and MHC-II expression by microglia, Th1 and Th17 T cell infiltrates, and VCAM-1+ endothelial cells and improved neurocognitive activity, without blocking graft-versus-leukemia effects. Consistent with these findings in mice, we observed increased activation and TNF production of microglia in the CNS of GVHD patients. In summary, we prove a role for microglia in CNS-GVHD, identify the TAK1/TNF/MHC-II axis as a mediator of CNS-GVHD, and provide a TAK1 inhibitor-based approach against GVHD-induced neurotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.