Abstract：
:Mechanisms that degrade inflammatory mRNAs are well known; however, stabilizing mechanisms are poorly understood. Here, we show that Act1, an interleukin-17 (IL-17)-receptor-complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, the SEFIR-binding element (SBE), in the 3' untranslated region (UTR) of Cxcl1 mRNA, encoding an inflammatory chemokine. mRNA-bound Act1 directs formation of three compartmentally distinct RNA-protein complexes (RNPs) that regulate three disparate events in inflammatory-mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P bodies and promoting translation. SBE RNA aptamers decreased IL-17-mediated mRNA stabilization in vitro, IL-17-induced skin inflammation and airway inflammation in a mouse asthma model, thus providing a therapeutic strategy for autoimmune diseases. These results reveal a network in which Act1 assembles RNPs on the 3' UTRs of select mRNAs and consequently controls receptor-mediated mRNA stabilization and translation during inflammation.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Herjan T,Hong L,Bubenik J,Bulek K,Qian W,Liu C,Li X,Chen X,Yang H,Ouyang S,Zhou H,Zhao J,Vasu K,Cockman E,Aronica M,Asosingh K,Licatalosi DD,Qin J,Fox PL,Hamilton TA,Driscoll D,Li Xdoi
10.1038/s41590-018-0071-9subject
Has Abstractpub_date
2018-04-01 00:00:00pages
354-365issue
4eissn
1529-2908issn
1529-2916pii
10.1038/s41590-018-0071-9journal_volume
19pub_type
杂志文章abstract：:We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/79738
更新日期：2000-10-01 00:00:00
abstract：:Vaccines can have nonspecific effects through their modulation of responses to infections not specifically targeted by the vaccine. However, lack of knowledge about the underlying immunological mechanisms and molecular cause-and-effect relationships prevent use of this potentially powerful early-life intervention to i...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2961
更新日期：2014-10-01 00:00:00
abstract：:Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding pro...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-0697-2
更新日期：2020-08-01 00:00:00
abstract：:The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-019-0582-z
更新日期：2020-02-01 00:00:00
abstract：:Regulatory T cells (Treg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in Treg cells was dynamically influenced by the...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3053
更新日期：2015-02-01 00:00:00
abstract：:T cells compete in the response to antigen in vivo and this competition may drive the affinity maturation of a secondary T cell response. Here we show that high-affinity T cells out-competed lower affinity T cells during a response to antigenic challenge in vivo. Although competition between T cells specific for diffe...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni742
更新日期：2002-01-01 00:00:00
abstract：:Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In add...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.3273
更新日期：2015-10-01 00:00:00
abstract：:In T lymphocytes, the mitogen-activated protein kinase (MAPK) p38 regulates pleiotropic functions and is activated by canonical MAPK signaling or the alternative activation pathway downstream of the T cell antigen receptor (TCR). Here we found that senescent human T cells lacked the canonical and alternative pathways ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2981
更新日期：2014-10-01 00:00:00
abstract：:Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than th...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni801
更新日期：2002-06-01 00:00:00
abstract：:Autoreactive T cells are eliminated in the thymus to prevent autoimmunity by promiscuous expression of tissue-restricted self-antigens in medullary thymic epithelial cells. This expression is dependent on the transcription factor Fezf2, as well as the transcriptional regulator Aire, but the entire picture of the trans...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-0717-2
更新日期：2020-08-01 00:00:00
abstract：:T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth respo...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1193
更新日期：2005-05-01 00:00:00
abstract：:We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentati...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni875
更新日期：2003-01-01 00:00:00
abstract：:The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens. Here we show that ligation of the C-C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8 alpha+...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/76957
更新日期：2000-07-01 00:00:00
abstract：:Naturally arising CD25(+)CD4(+) regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish ...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1178
更新日期：2005-04-01 00:00:00
abstract：:After homing to lymph nodes, CD8+ T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinet...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1559
更新日期：2008-03-01 00:00:00
abstract：:The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-posit...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1123
更新日期：2004-11-01 00:00:00
abstract：: ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-018-0282-0
更新日期：2019-01-01 00:00:00
abstract：:FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3835
更新日期：2017-11-01 00:00:00
abstract：:Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, g...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.1935
更新日期：2010-10-01 00:00:00
abstract：:The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappaB; however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1563
更新日期：2008-03-01 00:00:00
abstract：:Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct pr...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-019-0403-4
更新日期：2019-07-01 00:00:00
abstract：:The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2341
更新日期：2012-06-03 00:00:00
abstract：:The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as t...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/s41590-020-00816-x
更新日期：2021-01-01 00:00:00
abstract：:The mechanisms that lead to inflammation after necrotic cell death are poorly understood. New data show that the C-type lectin Mincle is involved in this process. ...
journal_title：Nature immunology
pub_type： 评论,杂志文章,评审
doi：10.1038/ni1008-1099
更新日期：2008-10-01 00:00:00
abstract：:Macrophages infected with human immunodeficiency virus type 1 emit long intercellular conduits that shuttle the viral protein Nef to bystander B cells, where it impairs cellular function and immunoglobulin class switching. ...
journal_title：Nature immunology
pub_type： 新闻
doi：10.1038/ni0909-933
更新日期：2009-09-01 00:00:00
abstract：:The origin and specification of human dendritic cells (DCs) have not been investigated at the clonal level. Through the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34+ progenitor cells, we found ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3789
更新日期：2017-08-01 00:00:00
abstract：:Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific o...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3790
更新日期：2017-07-19 00:00:00
abstract：:Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter t...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.1897
更新日期：2010-08-01 00:00:00
abstract：:The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable recepto...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-018-0305-x
更新日期：2019-03-01 00:00:00
abstract：:Interactions driven by the T cell antigen receptor (TCR) determine the lineage fate of CD4(+)CD8(+) thymocytes, but the molecular mechanisms that induce the lineage-determining transcription factors are unknown. Here we found that TCR-induced transcription factors Egr2 and Egr1 had higher and more-prolonged expression...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2230
更新日期：2012-02-05 00:00:00
