Abstract:
:The variable lymphocyte receptors (VLRs) of jawless vertebrates such as lamprey and hagfish are composed of highly diverse modular leucine-rich repeats. Each lymphocyte assembles a unique VLR by rearrangement of the germline gene. In the lamprey genome, we identify here about 850 distinct cassettes encoding leucine-rich repeat modules that serve as sequence templates for the hypervariable VLR repertoires. The data indicate a gene conversion-like process in VLR diversification. Genomic analysis suggested a link between the VLR and platelet glycoprotein receptors. Lamprey lymphocytes express two putative deaminases of the AID-APOBEC family that may be involved in VLR diversification, as indicated by in vitro mutagenesis and recombination assays. Vertebrate acquired immunity could have therefore originated from lymphocyte receptor diversification by an ancestral AID-like DNA cytosine deaminase.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Rogozin IB,Iyer LM,Liang L,Glazko GV,Liston VG,Pavlov YI,Aravind L,Pancer Zdoi
10.1038/ni1463subject
Has Abstractpub_date
2007-06-01 00:00:00pages
647-56issue
6eissn
1529-2908issn
1529-2916pii
ni1463journal_volume
8pub_type
杂志文章abstract::Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2541
更新日期:2013-04-01 00:00:00
abstract::Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs RGYW and WA were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched WA were preferentially found in one DNA strand and RGYW hotspots were found in both strands. Analysis of base-substituti...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/88732
更新日期:2001-06-01 00:00:00
abstract::The immune response is orchestrated by a variety of immune cells. The function of each cell is determined by the collective signals from various immunoreceptors, whose expression and activity depend on the developmental stages of the cell and its environmental context. Recent studies have highlighted the presence of m...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0491-1
更新日期:2019-10-01 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::Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (T(FH) cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the T(H)17 subset of helper T cells in the lungs...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3008
更新日期:2014-11-01 00:00:00
abstract::The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functio...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3576
更新日期:2016-12-01 00:00:00
abstract::Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2215
更新日期:2012-01-29 00:00:00
abstract::Despite the prevalence and clinical importance of influenza, its long-term effect on lung immunity is unclear. Here we describe that following viral clearance and clinical recovery, at 1 month after infection with influenza, mice are better protected from Streptococcus pneumoniae infection due to a population of monoc...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0568-x
更新日期:2020-02-01 00:00:00
abstract::CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gen...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni759
更新日期:2002-02-01 00:00:00
abstract::Membrane recruitment of adaptor proteins is crucial for coupling antigen receptors to downstream signaling events. Despite the essential function of the B cell adaptor SLP-65, the mechanism of its recruitment to the plasma membrane is not yet understood. Here we show that a highly conserved leucine zipper in the SLP-6...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1163
更新日期:2005-02-01 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::Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties preprogrammed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription fact...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0737-y
更新日期:2020-09-01 00:00:00
abstract::CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release-activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans. Here we generated CRACM1-deficient mice in which beta-galactosidase activity 'reporte...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1550
更新日期:2008-01-01 00:00:00
abstract::In neutrophils, superoxide anion production generally accompanies chemotaxis and functions in killing invading pathogens. The GIT2 GTPase-activating protein binds to the guanine nucleotide-exchange factor alphaPIX. Here we show that GIT2 was necessary for directional chemotaxis and for the suppression of superoxide pr...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1349
更新日期:2006-07-01 00:00:00
abstract::The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a res...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0793-3
更新日期:2020-12-01 00:00:00
abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0544-5
更新日期:2019-12-01 00:00:00
abstract::TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 doub...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3630
更新日期:2017-01-01 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::Hematopoiesis requires tight regulation of the hematopoietic stem cell (HSC) population; however, the dynamics of HSC use at steady state are uncertain. Over 3-7 months, we evaluated the repopulation and self-renewal of more than 600 individual human 'severe combined immunodeficiency mouse-repopulating cells' (SRCs), ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1393
更新日期:2006-11-01 00:00:00
abstract::In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Suppl...
journal_title:Nature immunology
pub_type: 已发布勘误
doi:10.1038/s41590-018-0154-7
更新日期:2018-09-01 00:00:00
abstract::Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threa...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-00826-9
更新日期:2021-01-01 00:00:00
abstract::Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/87766
更新日期:2001-05-01 00:00:00
abstract::Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1303
更新日期:2006-02-01 00:00:00
abstract::CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue t...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-00850-9
更新日期:2021-01-11 00:00:00
abstract::The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1438
更新日期:2007-03-01 00:00:00
abstract::Tolerance to endotoxins that is triggered by prior exposure to Toll-like receptor (TLR) ligands provides a mechanism with which to dampen inflammatory cytokines. The receptor-interacting protein RIP140 interacts with the transcription factor NF-κB to regulate the expression of genes encoding proinflammatory cytokines....
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2238
更新日期:2012-03-04 00:00:00
abstract::In the version of this Research Highlight initially published, the url for the linked article was incorrect ( https://doi.org/10.1172/JCI90647JCI90647 ). The correct link is https://doi.org/10.1172/JCI90647 . The error has been corrected in the HTML and PDF versions of the article. ...
journal_title:Nature immunology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41590-018-0159-2
更新日期:2018-08-01 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
abstract::The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a To...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni955
更新日期:2003-08-01 00:00:00
abstract::Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alph...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1379
更新日期:2006-10-01 00:00:00