ArticleBlood2020
Pathogenic Bhlhe40+ GM-CSF+ CD4+ T cells promote indirect alloantigen presentation in the GI tract during GVHD.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Dynamic immune profiling enables early distinction between gastrointestinal GVHD and viral diarrhea after hematopoietic stem cell transplantation.BMC immunology · 2026Article
- Engineered CD40-biosensor-expressing Treg cells as a cell therapy approach for inflammatory diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Stem-like memory-T maintenance and differentiation into tissue-resident T cells sustain chronic graft-versus-host disease in mice.Nature communications · 2026Article
- Beyond HLA: an exploratory pilot study of non-HLA antibodies, HLA sensitization, and GSTT1 genotype in platelet transfusion refractoriness.Frontiers in immunology · 2026Article
- Evaluation of cyclophosphamide for steroid-refractory hepatic acute graft-vs-host disease after allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2026Article
- Retinoic acid regulates donor myeloid-derived suppressor cell and colonic dendrite cell reconstitution after allogeneic hematopoietic stem cell transplantation in mice.Frontiers in immunology · 2026Article
- IL-18 drives the Bhlhe40-mediated pathogenic Th17 cell response and exacerbates autoimmune disease progression.Cellular & molecular immunology · 2025Article
- Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease.Cell reports. Medicine · 2025Article
- Intestinal epithelium-derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease.Science translational medicine · 2025Article
- GM-CSFTheranostics · 2025Review
- Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Bhlhe40 limits early IL-10 production from CD4Infection and immunity · 2023Article
- Cutting Edge: STAT4 Promotes Bhlhe40 Induction to Drive Protective IFN-γ from NK Cells during Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- CD4+ T-cell subsets in autoimmune hepatitis: A review.Hepatology communications · 2023Review
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- Steady-state memory-phenotype conventional CD4Experimental & molecular medicine · 2023Article
- Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation.Cell reports · 2023Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Gastrointestinal (GI) tract involvement is the major cause of morbidity and mortality in acute graft-versus-host disease (GVHD), and pathological damage is largely attributable to inflammatory cytokine production. Recently, granulocyte-macrophage colony stimulating factor (GM-CSF) has been identified as a cytokine that mediates inflammation in the GI tract, but the transcriptional program that governs GM-CSF production and the mechanism by which GM-CSF links adaptive to innate immunity within this tissue site have not been defined. In the current study, we identified Bhlhe40 as a key transcriptional regulator that governs GM-CSF production by CD4+ T cells and mediates pathological damage in the GI tract during GVHD. In addition, we observed that GM-CSF was not regulated by either interleukin 6 (IL-6) or IL-23, which are both potent inducers of GVHD-induced colonic pathology, indicating that GM-CSF constitutes a nonredundant inflammatory pathway in the GI tract. Mechanistically, GM-CSF had no adverse effect on regulatory T-cell reconstitution, but linked adaptive to innate immunity by enhancing the activation of donor-derived dendritic cells in the colon and subsequent accumulation of these cells in the mLNs. In addition, GM-CSF promoted indirect alloantigen presentation, resulting in the accumulation of donor-derived T cells with a proinflammatory cytokine phenotype in the colon. Thus, Bhlhe40+ GM-CSF+ CD4+ T cells constitute a colitogenic T-cell population that promotes indirect alloantigen presentation and pathological damage within the GI tract, positioning GM-CSF as a key regulator of GVHD in the colon and a potential therapeutic target for amelioration of this disease.
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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.