Abstract:
:Cytosolic detection of pathogen-derived nucleic acids is critical for the initiation of innate immune defense against diverse bacterial, viral and eukaryotic pathogens. Conversely, inappropriate responses to cytosolic nucleic acids can produce severe autoimmune pathology. The host protein STING has been identified as a central signaling molecule in the innate immune response to cytosolic nucleic acids. STING seems to be especially critical for responses to cytosolic DNA and the unique bacterial nucleic acids called 'cyclic dinucleotides'. Here we discuss advances in the understanding of STING and highlight the many unresolved issues in the field.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Burdette DL,Vance REdoi
10.1038/ni.2491subject
Has Abstractpub_date
2013-01-01 00:00:00pages
19-26issue
1eissn
1529-2908issn
1529-2916pii
ni.2491journal_volume
14pub_type
杂志文章,评审abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature immunology
pub_type: 已发布勘误
doi:10.1038/s41590-020-00809-w
更新日期:2020-12-01 00:00:00
abstract::The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni922
更新日期:2003-05-01 00:00:00
abstract::Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-12), IL-4 and IL-6 are required for differentiation into the T(H)1, T(H)2 and T(H)17 subsets of helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls T(H)2 differentiation by regulating both t...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2030
更新日期:2011-06-01 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::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::Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is act...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1028
更新日期:2004-02-01 00:00:00
abstract::Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell a...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2928
更新日期:2014-08-01 00:00:00
abstract::T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects....
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1351
更新日期:2006-07-01 00:00:00
abstract::A fundamental puzzle in immunology is how the immune system decides what types of immune responses to launch against different stimuli. Although much is known about control of T helper type 1 (T(H)1) and T(H)17 responses, the mechanisms that initiate T(H)2 and T regulatory (T(reg)) responses remain obscure. Emerging s...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.1894
更新日期:2010-08-01 00:00:00
abstract::B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in hum...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0772-8
更新日期:2020-11-01 00:00:00
abstract::The actin cytoskeleton seems to play two critical roles in the activation of T cells. One of these roles is T cell shape development and movement, including formation of the immunological synapse. The other is the formation of a scaffold for signaling components. This review focuses on the recent convergence of cell b...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/76877
更新日期:2000-07-01 00:00:00
abstract::Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during ly...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1695
更新日期:2009-02-01 00:00:00
abstract::NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiv...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3853
更新日期:2017-12-01 00:00:00
abstract::The transcription factor Aire controls immunological tolerance by inducing the ectopic thymic expression of many tissue-specific genes, acting broadly by removing stops on the transcriptional machinery. To better understand Aire's specificity, we performed single-cell RNA-seq and DNA-methylation analysis of Aire-suffi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3247
更新日期:2015-09-01 00:00:00
abstract::The location of embryonic lymph node development is determined by the initial clustering of lymphoid tissue-inducer (LTi) cells. Here we demonstrate that both the chemokine CXCL13 and the chemokine CCL21 attracted LTi cells at embryonic days 12.5-14.5 and that initial clustering depended exclusively on CXCL13. Retinoi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1789
更新日期:2009-11-01 00:00:00
abstract::Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/82732
更新日期:2000-12-01 00:00:00
abstract::T cell exhaustion has a major role in failure to control chronic infection. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the t...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2046
更新日期:2011-05-29 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::Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni0502-427
更新日期:2002-05-01 00:00:00
abstract::Polarization of the T cell microtubule-organizing center (MTOC) toward the antigen-presenting cell (APC) is driven by the accumulation of diacylglycerol (DAG) at the immunological synapse (IS). The mechanisms that couple DAG to the MTOC are not known. By single-cell photoactivation of the T cell antigen receptor (TCR)...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2033
更新日期:2011-05-22 00:00:00
abstract::Although master transcription factors (TFs) are key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress the development of other, non-specific T cell lineages has not been fully elucidated. Through the use of regulatory T ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3667
更新日期:2017-03-01 00:00:00
abstract::Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells. However, the genetic evidence for this recombination pathway has been challenged. Furthermore, no molecular components that directly control V(H) gene rearrangement ha...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1226
更新日期:2005-08-01 00:00:00
abstract::The transcription factor c-Myb is expressed throughout T cell development in the thymus. However, little is understood about c-Myb function because of the embryonic lethality of traditional Myb-null mutations. Using tissue-specific deletion to abrogate c-Myb expression at distinct stages of T cell development, we iden...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1085
更新日期:2004-07-01 00:00:00
abstract::Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3319
更新日期:2016-02-01 00:00:00
abstract::Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1862
更新日期:2010-05-01 00:00:00
abstract::A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of l...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni778
更新日期:2002-05-01 00:00:00
abstract::Interleukin 17 (IL-17)-producing T helper 17 cells (T(H)-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T(H)-17 differentiation remain controversial. Using a syst...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1613
更新日期:2008-06-01 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::Deletion of the DNA-binding domain of the transcription factor Ikaros generates dominant-negative isoforms that interfere with its activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemia (B-ALL). Here we found that conditional inactivation of the Ikaros DNA-binding domain in e...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2821
更新日期:2014-03-01 00:00:00
abstract::CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previousl...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2568
更新日期:2013-05-01 00:00:00