ArticleThe Journal of clinical investigation2021
Graft-versus-host disease depletes plasmacytoid dendritic cell progenitors to impair tolerance induction.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- DC-CD4 bispecific tolerogenic nanovesicles induce antigen-specific regulatory T cells and ameliorate collagen-induced arthritis in mice.Nature communications · 2026Article
- Cellular therapies for the prevention and treatment of acute graft-versus-host disease.Stem cells (Dayton, Ohio) · 2025Review
- Leukocyte immunoglobulin-like receptor B4: A keystone in immune modulation and therapeutic target in cancer and beyond.Cancer innovation · 2024Review
- Oral Chronic Graft-Versus-Host Disease: Pathogenesis, Diagnosis, Current Treatment, and Emerging Therapies.International journal of molecular sciences · 2024Review
- Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.Journal of translational medicine · 2024Article
- Therapeutic Inducers of Natural Killer cell Killing (ThINKK): preclinical assessment of safety and efficacy in allogeneic hematopoietic stem cell transplant settings.Journal for immunotherapy of cancer · 2024Article
- Therapeutic induction of antigen-specific immune tolerance.Nature reviews. Immunology · 2024Review
- The opposite impact of Janus kinase inhibitor Ruxolitinib on the function of bone marrow mesenchymal stem cells and immune cells in acute GVHD recipients.Blood science (Baltimore, Md.) · 2023Article
- Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut.Immunity, inflammation and disease · 2023Review
- Effects of immune system cells in GvHD and corresponding therapeutic strategies.Blood research · 2023Review
- Complex interactions of cellular players in chronic Graft-versus-Host Disease.Frontiers in immunology · 2023Review
- Article
- LILRB4, an immune checkpoint on myeloid cells.Blood science (Baltimore, Md.) · 2022Review
- Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model.Frontiers in immunology · 2022Review
- Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation.Respiratory research · 2021Article
- National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report.Transplantation and cellular therapy · 2021Review
- Article
- Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer.Antibody therapeutics · 2021Review
- Bone Marrow Regulatory T Cells Are a Unique Population, Supported by Niche-Specific Cytokines and Plasmacytoid Dendritic Cells, and Required for Chronic Graft-Versus-Host Disease Control.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Graft-versus-host disease (GVHD) causes failed reconstitution of donor plasmacytoid dendritic cells (pDCs) that are critical for immune protection and tolerance. We used both murine and human systems to uncover the mechanisms whereby GVHD induces donor pDC defects. GVHD depleted Flt3-expressing donor multipotent progenitors (MPPs) that sustained pDCs, leading to impaired generation of pDCs. MPP loss was associated with decreased amounts of MPP-producing hematopoietic stem cells (HSCs) and oxidative stress-induced death of proliferating MPPs. Additionally, alloreactive T cells produced GM-CSF to inhibit MPP expression of Tcf4, the transcription factor essential for pDC development, subverting MPP production of pDCs. GM-CSF did not affect the maturation of pDC precursors. Notably, enhanced recovery of donor pDCs upon adoptive transfer early after allogeneic HSC transplantation repressed GVHD and restored the de novo generation of donor pDCs in recipient mice. pDCs suppressed the proliferation and expansion of activated autologous T cells via a type I IFN signaling-dependent mechanism. They also produced PD-L1 and LILRB4 to inhibit T cell production of IFN-γ. We thus demonstrate that GVHD impairs the reconstitution of tolerogenic donor pDCs by depleting DC progenitors rather than by preventing pDC maturation. MPPs are an important target to effectively bolster pDC reconstitution for controlling GVHD.
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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.