ArticleJCI insight2019
Stress responses, M2 macrophages, and a distinct microbial signature in fatal intestinal acute graft-versus-host disease.
Article in JCI insight, 2019. 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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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.Clinical and experimental medicine · 2025Review
- Identification and validation of tissue-based gene biomarkers for acute intestinal graft-versus-host disease(AIGVHD).Frontiers in immunology · 2025Article
- Leveraging machine learning for predicting acute graft-versus-host disease grades in allogeneic hematopoietic cell transplantation for T-cell prolymphocytic leukaemia.BMC medical research methodology · 2024Article
- Amphiregulin as a biomarker for monitoring lifethreatening acute graft-Haematologica · 2024Article
- Unveiling amphiregulin: a blood-based biomarker for graft-Haematologica · 2024Article
- Article
- Article
- Transcriptome analysis in acute gastrointestinal graft-Haematologica · 2023Article
- Recent advances in graft-versus-host disease.Faculty reviews · 2023Review
- Article
- Therapeutic targeting of endoplasmic reticulum stress in acute graft-Haematologica · 2022Article
- High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease.Journal of cutaneous pathology · 2022Article
- Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model.Frontiers in immunology · 2022Review
- Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation.Handbook of experimental pharmacology · 2022Article
- Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice.Frontiers in oncology · 2022Article
- Recipient Tregs: Can They Be Exploited for Successful Hematopoietic Stem Cell Transplant Outcomes?Frontiers in immunology · 2022Review
- Acute GVHD: think before you treat.Hematology. American Society of Hematology. Education Program · 2021Review
- Donor-derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation.Immunity, inflammation and disease · 2021Article
- Macrophage regulation of graft-World journal of clinical cases · 2020Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 7 countries.
Funding
Abstract
Steroid-refractory intestinal acute graft-versus-host disease (aGVHD) is a frequently fatal condition with little known about mechanisms driving failed steroid responses in gut mucosa. To uncover novel molecular insights in steroid-refractory aGVHD, we compared gene expression profiles of rectosigmoid biopsies from patients at diagnosis of clinical stage 3-4 lower intestinal aGVHD (N=22), to repeat biopsies when the patients became steroid refractory (N=22), and normal controls (N=10). We also performed single gene analyses of factors associated with tolerance (programmed death ligand-1 [PDL1], indoleamine 2,3 dioxygenase [IDO1], and T cell immunoreceptor with Ig and ITIM domains [TIGIT]) and found that significantly higher expression levels of these aGVHD inhibitory genes (PDL1, IDO1, TIGIT) at aGVHD onset became decreased in the steroid-refractory state. We examined genes triggered by microbial ligands to stimulate gut repair, amphiregulin (AREG) and the aryl hydrocarbon receptor (AhR), and found that both AREG and AhR gene expression levels were increased at aGVHD onset and remained elevated in steroid-refractory aGVHD. We also identified higher expression levels of metallothioneines, metal-binding enzymes induced in stress responses, and M2 macrophage genes in steroid-refractory aGVHD. We observed no differences in T-cell subsets between onset and steroid-refractory aGVHD. Patients with a rapidly fatal course showed greater DNA damage and a distinct microbial signature at aGVHD onset, whereas patients with more prolonged survival exhibited a gene expression profile consistent with activation of Smoothened. Our results extend the paradigm beyond T cell-centric therapies for steroid-refractory GI aGVHD and highlight new mechanisms for therapeutic exploration.
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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.