Abstract:
:Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such as MyD88-IRAK4 or TLR3-Unc93b-TRIF-TRAF3, have demonstrated the specific roles of these pathways in host defense against pyogenic bacteria and herpesviruses, respectively. Second, common polymorphisms in genes encoding several TLRs and associated genes have been associated with both infectious and autoimmune diseases. The study of genetic variation in TLRs in various populations combined with information on infection has demonstrated complex interaction between genetic variation in TLRs and environmental factors. This interaction explains the differences in the effect of TLR polymorphisms on susceptibility to infection and autoimmune disease in various populations.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Netea MG,Wijmenga C,O'Neill LAdoi
10.1038/ni.2284subject
Has Abstractpub_date
2012-05-18 00:00:00pages
535-42issue
6eissn
1529-2908issn
1529-2916pii
ni.2284journal_volume
13pub_type
杂志文章,评审abstract::Weak T cell antigen receptor (TCR) signals from contact with self ligands act in synergy with antiapoptotic signals induced by interleukin 7 (IL-7) to promote the survival of naive T cells in a resting state. The amount of background TCR signaling in naive T cells is set by post-thymic TCR tuning and operates at an in...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2018
更新日期:2011-06-01 00:00:00
abstract::High-dose radiation activates caspases in tumor cells to produce abundant DNA fragments for DNA sensing in antigen-presenting cells, but the intrinsic DNA sensing in tumor cells after radiation is rather limited. Here we demonstrate that irradiated tumor cells hijack caspase 9 signaling to suppress intrinsic DNA sensi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0641-5
更新日期:2020-05-01 00:00:00
abstract::Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB) kinase (IKK) complex, which governs NF-κB-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2137
更新日期:2011-10-30 00:00:00
abstract::Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17-producing T helper (TH-17) differentiation can differentially regulate the glycosyl...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1482
更新日期:2007-08-01 00:00:00
abstract::Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3200
更新日期:2015-07-01 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::Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-re...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0430-1
更新日期:2019-08-01 00:00:00
abstract::Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expressio...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3714
更新日期:2017-05-01 00:00:00
abstract::Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR)...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/86302
更新日期:2001-04-01 00:00:00
abstract::Feedback regulatory circuits provided by regulatory T cells (T(reg) cells) and suppressive cytokines are an intrinsic part of the immune system, along with effector functions. Here we discuss some of the regulatory cytokines that have evolved to permit tolerance to components of self as well as the eradication of path...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2406
更新日期:2012-10-01 00:00:00
abstract::The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immuno...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2796
更新日期:2014-02-01 00:00:00
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-ri...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1463
更新日期:2007-06-01 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::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 17 (IL-17) is important in infection and autoimmunity; how it signals remains poorly understood. In this study, we identified the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP2...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2427
更新日期:2012-11-01 00:00:00
abstract::Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adapto...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2888
更新日期:2014-06-01 00:00:00
abstract::Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an exp...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1534
更新日期:2008-01-01 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::Antibody specificity and diversity is generated in B cells during germinal center maturation through clonal expansion while they undergo class-switch recombination and somatic hypermutation. Here we demonstrate that the transcriptional repressor Bcl-6 mediates this phenotype by directly repressing ATR in centroblasts ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1478
更新日期:2007-07-01 00:00:00
abstract::Transcriptome profiling is widely used to infer functional states of specific cell types, as well as their responses to stimuli, to define contributions to physiology and pathophysiology. Focusing on microglia, the brain's macrophages, we report here a side-by-side comparison of classical cell-sorting-based transcript...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0110-6
更新日期:2018-06-01 00:00:00
abstract::CD11b(+) dendritic cells (DCs) seem to be specialized for presenting antigens via major histocompatibility (MHC) class II complexes to stimulate helper T cells, but the genetic and regulatory basis for this is not established. Conditional deletion of Irf4 resulted in loss of CD11b(+) DCs, impaired formation of peptide...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2795
更新日期:2014-02-01 00:00:00
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/s41590-019-0531-x
更新日期:2019-11-01 00:00:00
abstract::Stimulation of Toll-like receptors (TLRs) initiates potent innate immune responses through Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88 and Trif. Analysis of Trif-deficient mice has shown that TLR3-dependent activation of the transcription factor NF-kappa B by the TLR3 ligand double-stran...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1061
更新日期:2004-05-01 00:00:00
abstract::The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the TH17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were ess...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3632
更新日期:2017-01-01 00:00:00
abstract::The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (m...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0083-5
更新日期:2018-05-01 00:00:00
abstract::Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it see...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2060
更新日期:2011-07-19 00:00:00
abstract::T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a transcriptional repressor that is a 'master regulator' of ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1321
更新日期:2006-05-01 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:: ...
journal_title:Nature immunology
pub_type: 评论,杂志文章
doi:10.1038/s41590-018-0302-0
更新日期:2019-02-01 00:00:00
abstract::Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional amo...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0598-4
更新日期:2020-03-01 00:00:00