Abstract:
:Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP) thymocytes. While RORγ antagonists are currently being developed to treat autoimmunity, it remains unclear how RORγT inhibition may impact thymocyte development. In this study, we show that in addition to regulating DP thymocytes survival, RORγT also controls genes that regulate thymocyte migration, proliferation, and T cell receptor (TCR)α selection. Strikingly, pharmacological inhibition of RORγ skews TCRα gene rearrangement, limits T cell repertoire diversity, and inhibits development of autoimmune encephalomyelitis. Thus, targeting RORγT not only inhibits Th17 cell development and function but also fundamentally alters thymic-emigrant recognition of self and foreign antigens. The analysis of RORγ inhibitors has allowed us to gain a broader perspective of the diverse function of RORγT and its impact on T cell biology.
journal_name
Cell Repjournal_title
Cell reportsauthors
Guo Y,MacIsaac KD,Chen Y,Miller RJ,Jain R,Joyce-Shaikh B,Ferguson H,Wang IM,Cristescu R,Mudgett J,Engstrom L,Piers KJ,Baltus GA,Barr K,Zhang H,Mehmet H,Hegde LG,Hu X,Carter LL,Aicher TD,Glick G,Zaller D,Hawwardoi
10.1016/j.celrep.2016.11.073subject
Has Abstractpub_date
2016-12-20 00:00:00pages
3206-3218issue
12issn
2211-1247pii
S2211-1247(16)31647-3journal_volume
17pub_type
杂志文章相关文献
Cell Reports文献大全abstract::The patterns of neuronal connectivity underlying multisensory integration, a fundamental property of many brains, remain poorly characterized. The Drosophila melanogaster mushroom body-an associative center-is an ideal system to investigate how different sensory channels converge in higher order brain centers. The neu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108138
更新日期:2020-09-15 00:00:00
abstract::Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undifferentiated cells and...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.08.086
更新日期:2015-10-13 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we cr...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.08.042
更新日期:2013-10-17 00:00:00
abstract::In contrast to our extensive knowledge on covalent small ubiquitin-like modifier (SUMO) target proteins, we are limited in our understanding of non-covalent SUMO-binding proteins. We identify interactors of different SUMO isoforms-monomeric SUMO1, monomeric SUMO2, or linear trimeric SUMO2 chains-using a mass spectrome...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2021.108691
更新日期:2021-01-26 00:00:00
abstract::CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the interplay of both cell types and their role in tumor suppression still remain elusive. In this study, we investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse mo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.10.086
更新日期:2016-11-22 00:00:00
abstract::Synapse formation is a complex process that involves the recruitment and assembly of a myriad of pre- and postsynaptic proteins. Despite being present at every synapse in the vertebrate CNS, little is known about the transport, recruitment, and stabilization of synapsin at nascent synapses during development. We exami...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.03.031
更新日期:2013-04-25 00:00:00
abstract::CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient exp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.05.061
更新日期:2019-06-18 00:00:00
abstract::A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.003
更新日期:2012-10-25 00:00:00
abstract::Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. We report an investigation in cellular targets of IL-38 during the progression of ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.03.082
更新日期:2019-04-16 00:00:00
abstract::Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore, it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, w...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.05.015
更新日期:2013-06-27 00:00:00
abstract::Meiotic progression in S. pombe is regulated by stage-specific gene expression and translation, changes in RNA stability, expression of anti-sense transcripts, and targeted proteolysis of regulatory proteins. We have used SILAC labeling to examine the relative levels of proteins in diploid S. pombe cells during meiosi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.12.075
更新日期:2019-01-22 00:00:00
abstract::Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.050
更新日期:2018-03-06 00:00:00
abstract::In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, de...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.06.025
更新日期:2014-07-24 00:00:00
abstract::Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expressi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.09.059
更新日期:2019-10-29 00:00:00
abstract::Nucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-tran...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.02.038
更新日期:2015-03-17 00:00:00
abstract::Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine....
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.05.022
更新日期:2018-06-12 00:00:00
abstract::The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.04.004
更新日期:2015-05-05 00:00:00
abstract::Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.063
更新日期:2017-11-07 00:00:00
abstract::Understanding how peptide selection is controlled on different major histocompatibility complex class I (MHC I) molecules is pivotal for determining how variations in these proteins influence our predisposition to infectious diseases, cancer, and autoinflammatory conditions. Although the intracellular chaperone TAPBPR...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.09.074
更新日期:2019-11-05 00:00:00
abstract::Lipoprotein cholesterol is delivered to the limiting membrane of late endosomes/lysosomes (LELs) by Niemann-Pick C1 (NPC1). However, the mechanism of cholesterol transport from LELs to the endoplasmic reticulum (ER) is poorly characterized. We report that oxysterol-binding protein-related protein 1L (ORP1L) is necessa...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.028
更新日期:2017-05-30 00:00:00
abstract::The enteroinvasive bacterium Shigella flexneri forces its uptake into non-phagocytic host cells through the translocation of T3SS effectors that subvert the actin cytoskeleton. Here, we report de novo actin polymerization after cellular entry around the bacterium-containing vacuole (BCV) leading to the formation of a ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107638
更新日期:2020-05-12 00:00:00
abstract::Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.112
更新日期:2018-05-29 00:00:00
abstract::Allergic asthma is a highly prevalent airway disease triggered by hyperresponsiveness to inhaled allergens. Interferon regulatory factor 7 (IRF7) has been shown to be highly expressed in nasal aspirates from children with asthma. Type 2 innate lymphoid cells (ILC2s) represent the major player in allergic airway inflam...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.077
更新日期:2019-11-26 00:00:00
abstract::Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit neutralizing responses against HIV-1 strains closely related to the immunizing trimer. However, to date such stabilization has succeeded with only a limited number of HIV-1 strains. To address this issue, here we develop ADROITri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108432
更新日期:2020-11-24 00:00:00
abstract::Maintenance of skeletal muscle mass requires a dynamic balance between protein synthesis and tightly controlled protein degradation by the calpain, autophagy-lysosome, and ubiquitin-proteasome systems (proteostasis). Several sensing and gene-regulatory mechanisms act together to maintain this balance in response to ch...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.017
更新日期:2018-07-03 00:00:00
abstract::Pancreatitis is an inflammatory disease of the exocrine pancreas and ranks among the most common gastrointestinal disorders. Inflamed tissues frequently experience conditions of insufficient oxygen availability, or hypoxia. Here, we demonstrate that hypoxia and consequent stabilization of the hypoxia-inducible factor ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.05.071
更新日期:2018-06-19 00:00:00
abstract::A mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) typically expresses one allele of one odorant receptor (OR) gene. It is widely thought that the great majority of the 1,141 intact mouse OR genes are expressed in one of four MOE zones (or bands or stripes), which are largely non-overlappin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.110
更新日期:2020-03-24 00:00:00
abstract::Major depressive disorder is associated with weight loss and decreased appetite; however, the signaling that connects these conditions is unclear. Here, we show that MC4R signaling in the dorsal raphe nucleus (DRN) affects feeding, anxiety, and depression. DRN infusion of α-MSH decreases DRN neuronal activation and fe...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108267
更新日期:2020-10-13 00:00:00
abstract::The plasma membrane (PM) forms extensive close junctions with the cortical endoplasmic reticulum (cER) in many cell types, ranging from yeast to mammals. How cells modulate structural plasticity of ER-PM contacts to accommodate space-demanding cortical events is largely unknown. Here, we report a role for eisosome-dri...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.12.098
更新日期:2020-02-04 00:00:00
abstract::Recent evidence supports the presence of an L-glutamyl methyltransferase(s) in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as "acidic residue methyltransferase-1" (Armt1), an enzyme that specifically targets prolife...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.01.054
更新日期:2015-03-03 00:00:00