ArticleJournal of immunology (Baltimore, Md. : 1950)2015
PLZF regulates CCR6 and is critical for the acquisition and maintenance of the Th17 phenotype in human cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Mucosal-Associated Invariant T Cells: Origins, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Old versus new: upstream and downstream of promyelocytic leukemia zinc finger protein.Cancer gene therapy · 2025Review
- Investigation of the Molecular Mechanism of Asthma in Meishan Pigs Using Multi-Omics Analysis.Animals : an open access journal from MDPI · 2025Article
- Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.CNS & neurological disorders drug targets · 2025Review
- Dysregulated T-cell homeostasis and decreased CD30Heliyon · 2024Article
- Establishment of Murine Pregnancy Requires the Promyelocytic Leukemia Zinc Finger Transcription Factor.International journal of molecular sciences · 2024Article
- Insights into the tissue repair features of MAIT cells.Frontiers in immunology · 2024Review
- Human CCR6+ Th Cells Show Both an Extended Stable Gradient of Th17 Activity and Imprinted Plasticity.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Human CCR6bioRxiv : the preprint server for biology · 2023Article
- Cellular heterogeneity of circulating CD4Scientific reports · 2021Article
- ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells.Frontiers in immunology · 2021Review
- Cytokine Profile of CCR6Sovremennye tekhnologii v meditsine · 2021Article
- The Transcription Factor Promyelocytic Leukemia Zinc Finger Protein Is Associated With Expression of Liver-Homing Receptors on Human Blood CD56Hepatology communications · 2020Article
- CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.The Journal of clinical investigation · 2019Article
- DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis.Nature communications · 2019Article
- Using CRISPR/Cas9 engineering to generate a mouse with a conditional knockout allele for the promyelocytic leukemia zinc finger transcription factor.Genesis (New York, N.Y. : 2000) · 2019Article
- Elastic net-based prediction of IFN-β treatment response of patients with multiple sclerosis using time series microarray gene expression profiles.Scientific reports · 2019Article
- RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients.Nature communications · 2019Article
- Article
- The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis.Viruses · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Th17 cells, which express the chemokine receptor CCR6, are implicated in many immune-mediated disorders, such as psoriasis and multiple sclerosis. We found that expression levels of CCR6 on human effector/memory CD4(+) T cells reflect a continuum of Th17 differentiation. By evaluating the transcriptome in cells with increasing CCR6, we detected progressive upregulation of ZBTB16, which encodes the broad complex, tramtrack, bric-à-brac-zinc finger transcription factor promyelocytic leukemia zinc finger protein (PLZF). Using chromatin immunoprecipitation for modified histones, p300, and PLZF, we identified enhancer-like sites at -9/-10 and -13/-14 kb from the upstream transcription start site of CCR6 that bind PLZF in CCR6(+) cells. For Th cells from adult blood, both in the CCR6(+) memory population and in naive cells activated ex vivo, knockdown of ZBTB16 downregulated CCR6 and other Th17-associated genes. ZBTB16 and RORC (which encodes the "master regulator" RORγt) cross-regulate each other, and PLZF binds at the RORC promoter in CCR6(+) cells. In naive Th cells from cord blood, ZBTB16 expression was confined to CD161(+) cells, which are Th17 cell precursors. ZBTB16 was not expressed in mouse Th17 cells, and Th17 cells could be made from luxoid mice, which harbor an inactivating mutation in Zbtb16. These studies demonstrate a role for PLZF as an activator of transcription important both for Th17 differentiation and the maintenance of the Th17 phenotype in human cells, expand the role of PLZF as a critical regulator in the human adaptive immune system, and identify a novel, essential element in a regulatory network that is of significant therapeutic interest.
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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.