ArticleBlood2022
Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109A induce less graft-versus-host disease.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 47 citations in OpenAlex.
- The prebiotic effects of soluble dietary fiber mixture on renal anemia and the gut microbiota in end-stage renal disease patients on maintenance hemodialysis: a prospective, randomized, placebo-controlled study.Journal of translational medicine · 2022Trial
- Modulation of the gut microbiota by traditional Chinese medicine to attenuate chemotherapy-induced toxicity in gastric cancer: a review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- Review
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
- Paradigm Shift of Microbiota-gut-brain Axis During Aging: Potential Role of Probiotics to Improve Cognitive Decline.Probiotics and antimicrobial proteins · 2026Review
- The Gut-Bone Marrow Axis: Deciphering the Mechanistic Impact of Microbial Metabolites on Hematopoietic Homeostasis and Disorders.Microorganisms · 2026Review
- Immunosenescence and Vaccine Efficacy in Aging: Dynamic Interplay of Gut Microbiota and mTOR Signaling Pathways.Aging cell · 2026Review
- The gut microbiome in solid-organ and haematopoietic-stem-cell transplantation.Nature reviews. Microbiology · 2026Review
- Short-chain fatty acids in ulcerative colitis: integrating metabolic fate, dynamic biomarkers, and precision delivery.Frontiers in nutrition · 2026Review
- Role of gut microbiome in suppression of cancers.Gut microbes · 2025Review
- Article
- Gut microbiota and acute graft-versus-host disease.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- The Mediating Role of Bioactive Molecules in Gut Microbiota-Bone Metabolism Crosstalk.Nutrients · 2025Review
- A Review of Nutritional Regulation of Intestinal Butyrate Synthesis: Interactions Between Dietary Polysaccharides and Proteins.Foods (Basel, Switzerland) · 2025Review
- The Gut Microbiota-Sex-Immunity Axis in Non-Communicable Diseases.Life (Basel, Switzerland) · 2025Review
- Selected Protective Mechanisms of Human Milk Against Intestinal Protozoal Infections in Infants.Current issues in molecular biology · 2025Review
- A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.Journal of clinical medicine · 2025Review
- Identification and validation of tissue-based gene biomarkers for acute intestinal graft-versus-host disease(AIGVHD).Frontiers in immunology · 2025Article
- Review
- Role of the microbiota in response to and recovery from cancer therapy.Nature reviews. Immunology · 2024Review
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
The intestinal microbiota is essential for the fermentation of dietary fiber into short-chain fatty acids (SCFA) such as butyrate, acetate, and propionate. SCFAs can bind to the G-protein-coupled receptors GPR43 and GPR109A (HCAR2), with varying affinities to promote cellular effects in metabolism or changes in immune function. We explored the role of GPR109A as the main receptor for butyrate in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Deletion of GPR109A in allo-HCT recipients did not affect GVHD, but transplantation of T cells from GPR109A knockout (KO) (Gpr109a-/-) mice into allo-HCT recipient mice significantly reduced GVHD morbidity and mortality compared with recipients of wild-type (WT) T cells. Recipients of Gpr109a-/- T cells exhibited less GVHD-associated target organ pathology and decreased proliferation and homing of alloreactive T cells to target tissues. Although Gpr109a-/- T cells did not exhibit immune deficits at a steady state, following allo-activation, Gpr109a-/- T cells underwent increased apoptosis and were impaired mitochondrial oxidative phosphorylation, which was reversible through antioxidant treatment with N-acetylcysteine (NAC). In conclusion, we found that GPR109A expression by allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary features to induce GVHD after allo-HCT.
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