ArticleThe Journal of clinical investigation2022
IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 22 citations in OpenAlex.
- A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD.Annals of hematology · 2025Trial
- Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential.Nature reviews. Immunology · 2026Review
- Development of 2‑Methyl-5-phenylpyrrolidine-Based ST2 Inhibitors for Neuroinflammatory Conditions.ACS medicinal chemistry letters · 2026Article
- Autoantibody-Based Models for the Diagnosis and Activity Assessment of Takayasu Arteritis.Journal of cardiovascular translational research · 2026Article
- Proinflammatory bone marrow niches and neutrophil activation are associated with TIGIT expression in multiple myeloma.Annals of hematology · 2025Article
- Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors.Biomedicines · 2025Review
- The effects of interleukin-21 in the biology of transplant rejection.Frontiers in immunology · 2025Review
- Dysregulated Treg repair responses lead to chronic rejection after heart transplantation.The Journal of clinical investigation · 2024Article
- Studies of Structure-Activity Relationship of 2-(Pyrrolidin-1ylmethyl)-1ACS medicinal chemistry letters · 2024Article
- Article
- Extracellular release of damaged mitochondria induced by prehematopoietic stem cell transplant conditioning exacerbates GVHD.Blood advances · 2024Article
- Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation.Nature communications · 2024Article
- Review
- Graft-Versus-Host Disease: Can Biomarkers Assist in Differential Diagnosis, Prognosis, and Therapeutic Strategy?Pharmaceuticals (Basel, Switzerland) · 2024Review
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- The graft versus leukemia effect: donor lymphocyte infusions and cellular therapy.Frontiers in immunology · 2024Review
- Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology.Science advances · 2023Article
- Tregs in transplantation tolerance: role and therapeutic potential.Frontiers in transplantation · 2023Review
- Review
- Graft-versus-host disease: establishing IL-33 as an important costimulatory molecule.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell-derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12-independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.
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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 Socratic graph.