Abstract:
:Regulatory T (Treg) cells expressing the transcription factor Foxp3 play an important role in maintaining immune homeostasis. Chronic inflammation is associated with reduced Foxp3 expression, function, and loss of phenotypic stability. Previous studies have established the importance of TNF receptor 2 (TNFR2) in the generation and/or activation of Treg cells. In this study, we assess the importance of TNFR2 in healthy mice and under inflammatory conditions. Our findings reveal that, in health, TNFR2 is important not only for the generation of Treg cells, but also for regulating their functional activity. We also show that TNFR2 maintains Foxp3 expression in Treg cells by restricting DNA methylation at the Foxp3 promoter. In inflammation, loss of TNFR2 results in increased severity and chronicity of experimental arthritis, reduced total numbers of Treg cells, reduced accumulation of Treg cells in inflamed joints, and loss of inhibitory activity. In addition, we demonstrate that, under inflammatory conditions, loss of TNFR2 causes Treg cells to adopt a proinflammatory Th17-like phenotype. It was concluded that TNFR2 signaling is required to enable Treg cells to promote resolution of inflammation and prevent them from undergoing dedifferentiation. Consequently, TNFR2-specific agonists or TNF1-specific antagonists may be useful in the treatment of autoimmune disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Tseng WY,Huang YS,Clanchy F,McNamee K,Perocheau D,Ogbechi J,Luo SF,Feldmann M,McCann FE,Williams ROdoi
10.1073/pnas.1909687116subject
Has Abstractpub_date
2019-10-22 00:00:00pages
21666-21672issue
43eissn
0027-8424issn
1091-6490pii
1909687116journal_volume
116pub_type
杂志文章abstract::Heterochromatin protein 1 (HP1), first discovered in Drosophila melanogaster, is a highly conserved chromosomal protein implicated in both heterochromatin formation and gene silencing. We report here characterization of an HP1-interacting protein, heterochromatin protein 2 (HP2), which codistributes with HP1 in the pe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.212458899
更新日期:2002-10-29 00:00:00
abstract::The activation of Janus kinases (JAKs) is crucial for propagation of the proliferative response initiated by many cytokines. The proliferation of various cell lines, particularly those of hematopoietic origin, is also modulated by mediators of oxidative stress such as nitric oxide and thiol redox reagents. Herein we d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.1.126
更新日期:1998-01-06 00:00:00
abstract::The complete nucleotide sequences of the cDNAs encoding the heavy- and light-chain variable regions (VH and VL) of myeloma protein W3129, an anti-alpha(1----6)-dextran with a unique combining site, have been determined. The VH region is encoded by a germ-line gene highly homologous to VH441, which also appears to be u...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.8.2440
更新日期:1987-04-01 00:00:00
abstract::Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.2.791
更新日期:1979-02-01 00:00:00
abstract::Soil bacteria and fungi play key roles in the functioning of terrestrial ecosystems, yet our understanding of their responses to climate change lags significantly behind that of other organisms. This gap in our understanding is particularly true for drylands, which occupy ∼41% of Earth´s surface, because no global, sy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1516684112
更新日期:2015-12-22 00:00:00
abstract::Aggregation of the receptor for IgE on mast cells, basophils, and a tumor analog, rat basophilic leukemia (RBL) cells, induces a calcium-dependent degranulation of the cells. We have measured the membrane potential (delta psi) of RBL cells during this reaction by using the tetraphenylphosphonium ion (Ph4P+) equilibrat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.18.5744
更新日期:1983-09-01 00:00:00
abstract::Ski8p is implicated in degradation of non-poly(A) and double-stranded RNA, and in meiotic DNA recombination. We have identified the Sordaria macrospora SKI8 gene. Ski8p is cytoplasmically localized in all vegetative and sexual cycle cells, and is nuclear localized, specifically in early-mid-meiotic prophase, in tempor...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2034282100
更新日期:2003-10-28 00:00:00
abstract::A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance--wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1423952112
更新日期:2015-01-27 00:00:00
abstract::Extracellular growth and differentiation factors induce changes in gene expression in the nucleus by initiating a series of protein associations that alter the subcellular localization of intracellular signaling proteins. Initial events involve receptor homo- or heterodimerization and subsequent recruitment of cytosol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.10.4604
更新日期:1996-05-14 00:00:00
abstract::Protein Hal is a human gamma4 heavy-chain disease protein whose molecular weight is reduced from 55,000 to 25,000 in 6 M guanidine due to the lack of disulfide bonds between heavy chains. Studies of aminoacid sequence indicate that it contains a gap of about 240 residues, starting 10 residues from the N-terminal end a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.4.1073
更新日期:1973-04-01 00:00:00
abstract::DNA-based identification depends on the probability that two different individuals have the same phenotype, which is given by kinship theory. Together with the large and consistent body of evidence on human population structure, kinship theory provides a sound basis for forensic use of DNA markers. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.7.2556
更新日期:1992-04-01 00:00:00
abstract::Recently, the highly invasive Asian tiger mosquito, Aedes albopictus, rapidly displaced resident populations of the yellow fever mosquito, Aedes aegypti in the southeastern United States and in Bermuda. Although multiple mechanisms of competitive displacement have been hypothesized, recent evidence of cross-inseminati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1219599110
更新日期:2013-02-19 00:00:00
abstract::Transient Receptor Potential Melastatin-8 (TRPM8), a recently identified member of the transient receptor potential (TRP) family of ion channels, is activated by mild cooling and by chemical compounds such as the supercooling agent, icilin. Since cooling, possibly involving TRPM8 stimulation, diminishes injury-induced...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1217431110
更新日期:2013-04-30 00:00:00
abstract::Metabolic imaging of the relative amounts of reduced NADH and FAD and the microenvironment of these metabolic electron carriers can be used to noninvasively monitor changes in metabolism, which is one of the hallmarks of carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime, and subcellular m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0708425104
更新日期:2007-12-04 00:00:00
abstract::Bilateria are currently subdivided into three superclades: Deuterostomia, Ecdysozoa, and Lophotrochozoa. Within this new taxonomic frame, acoelomate Platyhelminthes, for a long time held to be basal bilaterians, are now considered spiralian lophotrochozoans. However, recent 18S rDNA [small subunit (SSU)] analyses have...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.172390199
更新日期:2002-08-20 00:00:00
abstract::Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme cataly...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504361102
更新日期:2005-11-22 00:00:00
abstract::Stress can either promote or impair learning and memory. Such opposing effects depend on whether synapses persist or decay after learning. Maintenance of new synapses formed at the time of learning upon neuronal network activation depends on the stress hormone-activated glucocorticoid receptor (GR) and neurotrophic fa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1903203116
更新日期:2019-06-25 00:00:00
abstract::This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2017086117
更新日期:2020-12-22 00:00:00
abstract::Membranes were purified from rat muscle by a differential centrifugation method that avoids the use of salt extraction or incubations at elevated temperature. Three populations of membrane-limited vesicles were defined having average densities of 1.112 (fraction I), 1.141 (fraction II), and 1.158 (fraction III) g/ml i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.1.34
更新日期:1977-01-01 00:00:00
abstract::Release of formylmethionine from the reticulocyte ribosomal substrate, f[(3)H]Met-tRNA.ribosome, is promoted by reticulocyte release factor (RF). The initial rate of this reaction is stimulated by GTP but inhibited by GDPCP. Formation of an RF.UA[(3)H]A(2).ribosome complex is a measure of the binding of reticulocyte R...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.8.2350
更新日期:1973-08-01 00:00:00
abstract::Among the 15 extracellular domains of the mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R), domain 11 has evolved a binding site for IGF2 to negatively regulate ligand bioavailability and mammalian growth. Despite the highly evolved structural loops of the IGF2:domain 11 binding site, affinity-enh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1513023113
更新日期:2016-05-17 00:00:00
abstract::Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1714986115
更新日期:2018-05-15 00:00:00
abstract::This paper is the second of three describing a two-fluid theory of binary liquid mixtures. The general theory presented in the preceding paper is used to derive a model for calculating thermodynamic properties of hard-sphere mixtures. Calculations indicate that desirable boundary conditions are satisfied. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.16.5103
更新日期:1982-08-01 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein-Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic altera...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1705236114
更新日期:2017-09-05 00:00:00
abstract::Matching ATP:NADPH provision and consumption in the chloroplast is a prerequisite for efficient photosynthesis. In terms of ATP:NADPH ratio, the amount of ATP generated from the linear electron flow does not meet the demand of the Calvin-Benson-Bassham (CBB) cycle. Several different mechanisms to increase ATP availabi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1711497115
更新日期:2018-11-06 00:00:00
abstract::Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host-pathog...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1009080107
更新日期:2010-08-17 00:00:00
abstract::Forkhead box class O (FoxO) transcription factors are key regulators of growth, metabolism, life span, and stress resistance. FoxOs integrate signals from different pathways and guide the cellular response to varying energy and stress conditions. FoxOs are modulated by several signaling pathways, e.g., the insulin-TOR...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803022105
更新日期:2008-09-30 00:00:00
abstract::Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1808507115
更新日期:2018-12-18 00:00:00
abstract::The neural cell adhesion molecule (NCAM) is a membrane-associated member of the immunoglobulin superfamily capable of both homophilic and heterophilic binding. To investigate the significance of this binding, a gene targeting strategy in embryonic stem (ES) cells was used to replace the membrane-associated forms of NC...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.13.6421
更新日期:1996-06-25 00:00:00
abstract::Argonaute (Ago) proteins are the key component of the RNA-induced silencing complex and mediate RNA interference (RNAi) in association with small RNAs. Although overall the mechanism of RNAi is well understood, many molecular details of this complex process are not. Here we report about in-depth steady-state and, in p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1217838110
更新日期:2013-10-29 00:00:00