ArticleBlood2011
Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- The Number of Donor-Specific IL-21 Producing Cells Before and After Transplantation Predicts Kidney Graft Rejection.Frontiers in immunology · 2019Trial
- Article
- Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8Science translational medicine · 2021Article
- T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.Frontiers in immunology · 2021Review
- Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Central Roles of OX40L-OX40 Interaction in the Induction and Progression of Human T Cell-Driven Acute Graft-versus-Host Disease.ImmunoHorizons · 2019Article
- Choline acetyltransferase-expressing T cells are required to control chronic viral infection.Science (New York, N.Y.) · 2019Article
- Inflammatory Cytokine Networks in Gastrointestinal Tract Graft vs. Host Disease.Frontiers in immunology · 2019Review
- A potent immunomodulatory role of exosomes derived from mesenchymal stromal cells in preventing cGVHD.Journal of hematology & oncology · 2018Article
- Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
- MicroRNA in T-Cell Development and T-Cell Mediated Acute Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
- Evaluation of Serum Interleukin-21 and HLA-C1 Polymorphism in Pediatrician Hematopoietic Stem Cell Transplantation for Early Diagnosis of Acute Graft-Versus-Host DiseaseIranian biomedical journal · 2017Article
- Chitinase 3-Like-1-Deficient Splenocytes Deteriorated the Pathogenesis of Acute Graft-Versus-Host Disease via Regulating Differentiation of Tfh Cells.Inflammation · 2017Article
- Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells.Nature communications · 2017Article
- Article
- Serum miR-29a Is Upregulated in Acute Graft-versus-Host Disease and Activates Dendritic Cells through TLR Binding.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Conformal Nanoencapsulation of Allogeneic T Cells Mitigates Graft-versus-Host Disease and Retains Graft-versus-Leukemia Activity.ACS nano · 2016Article
- Translational opportunities for targeting the Th17 axis in acute graft-vs.-host disease.Mucosal immunology · 2016Review
- IL-21 Signaling in Immunity.F1000Research · 2016Review
- Umbilical cord blood-derived mesenchymal stem cells ameliorate graft-versus-host disease following allogeneic hematopoietic stem cell transplantation through multiple immunoregulations.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2015Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
IL-21 is a proinflammatory cytokine produced by Th17 cells. Abrogation of IL-21 signaling has recently been shown to reduce GVHD while retaining graft-versus-leukemia/lymphoma (GVL) responses. However, the mechanisms by which IL-21 may lead to a separation of GVHD and GVL remain incompletely understood. In a murine MHC-mismatched BM transplantation model, we observed that IL-21 receptor knockout (IL-21R KO) donor T cells mediate decreased systemic and gastrointestinal GVHD in recipients of a transplant. This reduction in GVHD was associated with expansion of transplanted donor regulatory T cells and with tissue-specific modulation of Th-cell function. IL-21R KO and wild-type donor T cells showed equivalent alloactivation, but IL-21R KO T cells showed decreased infiltration and inflammatory cytokine production within the mesenteric lymph nodes. However, Th-cell cytokine production was maintained peripherally, and IL-21R KO T cells mediated equivalent immunity against A20 and P815 hematopoietic tumors. In summary, abrogation of IL-21 signaling in donor T cells leads to tissue-specific modulation of immunity, such that gastrointestinal GVHD is reduced, but peripheral T-cell function and GVL capacity are retained. IL-21 is thus an exciting target for therapeutic intervention and improvement of clinical transplantation outcomes.
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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.