ArticleJournal of leukocyte biology2015
Epigenetic regulation of IL-12-dependent T cell proliferation.
Article in Journal of leukocyte biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer.Molecular therapy. Nucleic acids · 2024Article
- Bioinformatics analyses of potentially common pathogenic networks for primary Sjögren's syndrome complicated with acute myocardial infarction.Scientific reports · 2023Article
- The Chromatin Regulator Mll1 Supports T Follicular Helper Cell Differentiation by Controlling Expression of Bcl6, LEF-1, and TCF-1.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing.Biomedicines · 2023Review
- Differences in H3K4me3 and chromatin accessibility contribute to altered T-cell receptor signaling in neonatal naïve CD4 T cells.Immunology and cell biology · 2022Article
- Expression of leukotriene BCellular & molecular immunology · 2021Article
- Role of Epigenetics in the Regulation of Immune Functions of the Skin.The Journal of investigative dermatology · 2021Review
- Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis.Frontiers in immunology · 2021Article
- Epigenetic regulation of the PGE2 pathway modulates macrophage phenotype in normal and pathologic wound repair.JCI insight · 2020Article
- IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8Frontiers in immunology · 2020Article
- Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Regulation of T cell differentiation and function by epigenetic modification enzymes.Seminars in immunopathology · 2019Review
- Histone Methylation Directs Myeloid TLR4 Expression and Regulates Wound Healing following Cutaneous Tissue Injury.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Targeting epigenetic mechanisms in diabetic wound healing.Translational research : the journal of laboratory and clinical medicine · 2019Review
- The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Article
- IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification.Journal of inflammation research · 2017Article
- Inflammation: A Novel Therapeutic Target/Direction in Atherosclerosis.Current pharmaceutical design · 2017Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
It is well established that the cytokine IL-12 and the transcription factor STAT4, an essential part of the IL-12 signaling pathway, are critical components of the Th1 differentiation process in T cells. In response to pathogenic stimuli, this process causes T cells to proliferate rapidly and secrete high amounts of the cytokine IFN-γ, leading to the Th1 proinflammatory phenotype. However, there are still unknown components of this differentiation pathway. We here demonstrated that the expression of the histone methyltransferase Mll1 is driven by IL-12 signaling through STAT4 in humans and mice and is critical for the proper differentiation of a naïve T cell to a Th1 cell. Once MLL1 is up-regulated by IL-12, it regulates the proliferation of Th1 cells. As evidence of this, we show that Th1 cells from Mll1(+/-) mice are unable to proliferate rapidly in a Th1 environment in vitro and in vivo. Additionally, upon restimulation with cognate antigen Mll1(+/-), T cells do not convert to a Th1 phenotype, as characterized by IFN-γ output. Furthermore, we observed a reduction in IFN-γ production and proliferation in human peripheral blood stimulated with tetanus toxoid by use of a specific inhibitor of the MLL1/menin complex. Together, our results demonstrate that the MLL1 gene plays a previously unrecognized but essential role in Th1 cell biology and furthermore, describes a novel pathway through which Mll1 expression is regulated.
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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.