ArticleThe Journal of clinical investigation2015
IL-34 is a Treg-specific cytokine and mediates transplant tolerance.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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.
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Who cites it
60 citing papers in PubMed, 117 citations in OpenAlex.
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- Roles of IL-34 in neurological diseases: neuroprotection, inflammatory regulation, and myeloid plasticity.Frontiers in immunology · 2026Review
- IL-34 in neurological homeostasis and its multifaceted roles in central nervous system diseases.Frontiers in immunology · 2026Review
- CD8 regulatory T cell therapy in transplantation: a new path to clinical success?Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation.Life science alliance · 2025Article
- Role of IL-34 in Tumors and Its Application to Regulate Inflammation.Cancer science · 2025Review
- A donor PD-1Signal transduction and targeted therapy · 2025Article
- Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics.Signal transduction and targeted therapy · 2025Review
- Intestinal epithelium-derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease.Science translational medicine · 2025Article
- Characterization of novel CD8Cellular and molecular life sciences : CMLS · 2024Article
- IL-34 attenuates acute T cell-mediated rejection following renal transplantation by upregulating M2 macrophages polarization.Heliyon · 2024Article
- Renal graft function in transplanted patients correlates with CD45RC T cell phenotypic signature.PloS one · 2024Article
- Review
- Functional and transcriptional heterogeneity within the massively expanding HLADRJournal of virology · 2023Article
- CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential.Experimental & molecular medicine · 2023Review
- Initial exploration of a novel fusion protein, IL-4/IL-34/IL-10, which promotes cardiac allograft survival mice through alloregulation.Innate immunity · 2023Article
- Significance of IL-34 and SDC-1 in the pathogenesis of RA cells and preclinical models.Clinical immunology (Orlando, Fla.) · 2023Review
- Targeted Therapy of Interleukin-34 as a Promising Approach to Overcome Cancer Therapy Resistance.Cancers · 2023Review
- Multi-omics segregate different transcriptomic impacts of anti-IL-17A blockade on type 17 T-cells and regulatory immune cells in psoriasis skin.Frontiers in immunology · 2023Article
- Targeting regulatory T cells for cardiovascular diseases.Frontiers in immunology · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokines and metabolic pathway-controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non-IL-34-expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg-specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance.
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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.