Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function restraining methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 is heavily methylated when Blimp1 is ablated, leading to a loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.
Pubmed ID: 30759395 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsSoftware application that can be used for converting Eland, Maq (.map), BED or other files into WIG files and identifying areas of enrichment (ChIP-Seq analysis).
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Cd4-cre)1Cwi/BfluJ from IMSR.
View all literature mentionsMus musculus with name B6.129X-Foxp3tm4(YFP/cre)Ayr/StvAnuApb from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.129S1-Stat3tm1Xyfu/J from IMSR.
View all literature mentionsThis monoclonal targets CD126
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD126
View all literature mentionsThis monoclonal targets IL-10
View all literature mentionsThis monoclonal targets IFN-γ
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets IFN gamma
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets IL-17
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets CD90/CD90.1
View all literature mentionsThis monoclonal targets GITR
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets KLRG1
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets Foxp3
View all literature mentionsThis monoclonal targets IFN-γ
View all literature mentionsThis monoclonal targets IFN gamma
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets Foxp3
View all literature mentionsThis monoclonal targets IL-17
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets CD90/CD90.1
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets GITR
View all literature mentionsThis monoclonal targets KLRG1
View all literature mentionsThis monoclonal targets IL-10
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentions