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 gene superfamily--is predominantly expressed on CD25(+)CD4(+) T cells and on CD25(+)CD4(+)CD8(-) thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25(+)CD4(+) T cell-mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Shimizu J,Yamazaki S,Takahashi T,Ishida Y,Sakaguchi Sdoi
10.1038/ni759keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
135-42issue
2eissn
1529-2908issn
1529-2916pii
ni759journal_volume
3pub_type
杂志文章abstract::During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular s...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni836
更新日期:2002-10-01 00:00:00
abstract::More than 20 years after the first successful engraftment of human leukocytes and hematopoietic organs in mice, scientists met for the 2nd International Workshop on Humanized Mice to discuss progress and to highlight expectations in this dynamic field. ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1009-1039
更新日期:2009-10-01 00:00:00
abstract::Plasma cells are cellular factories devoted entirely to the manufacture and export of a single product: soluble immunoglobulin (Ig). As the final mediators of a humoral response, plasma cells play a critical role in adaptive immunity. Although intense effort has been devoted to studying the regulation and requirements...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1201-1103
更新日期:2001-12-01 00:00:00
abstract::Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human c...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1661
更新日期:2008-11-01 00:00:00
abstract:: ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0147-6
更新日期:2018-07-01 00:00:00
abstract::We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precur...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/89800
更新日期:2001-07-01 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/s41590-019-0545-4
更新日期:2019-12-01 00:00:00
abstract::High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, b...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2022
更新日期:2011-05-01 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::Antigen receptor-mediated production of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in lymphocytes triggers the release of Ca2+ from intracellular stores; this release of Ca2+ results in the opening of store-operated Ca2+ channels in the plasma membrane. Here we report that mice lacking Ins(1,4,5)P3 3-kinase B (Itpkb)...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1458
更新日期:2007-05-01 00:00:00
abstract::In the steady state, dendritic cells (DCs) in the lymph node induce T cell tolerance to self antigens. Innate signals trigger the maturation of tissue DCs, which migrate into lymph nodes and activate T cells. To examine DCs in vivo, we produced transgenic mice whose DCs expressed enhanced yellow fluorescent protein. T...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1139
更新日期:2004-12-01 00:00:00
abstract::The bidirectional interaction between the immune system and whole-body metabolism has been well recognized for many years. Via effects on adipocytes and hepatocytes, immune cells can modulate whole-body metabolism (in metabolic syndromes such as type 2 diabetes and obesity) and, reciprocally, host nutrition and commen...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.3466
更新日期:2016-05-19 00:00:00
abstract::Cysteinyl leukotrienes are established mediators of bronchial asthma and have agonist roles analogous to those of histamine in allergic rhinitis. We now know that the substance originally termed slow-reacting substance of anaphylaxis was composed of three cysteinyl leukotrienes that act in the inflammatory response vi...
journal_title:Nature immunology
pub_type: 历史文章,杂志文章
doi:10.1038/ni0208-113
更新日期:2008-02-01 00:00:00
abstract::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/77853
更新日期:2000-08-01 00:00:00
abstract::Activated T helper cells produce many cytokines, some of which are secreted through the immunological synapse toward the antigen-presenting cell. Here we have used immunocytochemistry, live-cell imaging and a surface-mediated secretion assay to show that there are two cytokine export pathways in T helper cells. Some c...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1304
更新日期:2006-03-01 00:00:00
abstract::Toxoplasma gondii is a common protozoan parasite that infects up to one third of the world's population. Notably, very little is known about innate immune sensing mechanisms for this obligate intracellular parasite by human cells. Here, by applying an unbiased biochemical screening approach, we show that human monocyt...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0250-8
更新日期:2019-01-01 00:00:00
abstract::The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1063
更新日期:2004-05-01 00:00:00
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-bind...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0071-9
更新日期:2018-04-01 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::The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, pr...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni907
更新日期:2003-04-01 00:00:00
abstract::An important function of receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs) is to regulate signaling by heterologous receptors. This review describes mechanisms by which ITAM-associated receptors modulate signaling by Toll-like receptors (TLRs), tumor necrosis factor receptor family ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.1706
更新日期:2009-04-01 00:00:00
abstract::HPK1 is a Ste20-related serine-threonine kinase that inducibly associates with the adaptors SLP-76 and Gads after T cell receptor (TCR) signaling. Here, HPK1 deficiency resulted in enhanced TCR-induced phosphorylation of SLP-76, phospholipase C-gamma1 and the kinase Erk, more-persistent calcium flux, and increased pro...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1416
更新日期:2007-01-01 00:00:00
abstract::Myxoma virus, a member of the poxvirus family, causes lethal infection only in rabbits, but the mechanism underlying the strict myxoma virus species barrier is not known. Here we show that myxoma virus infection of primary mouse embryo fibroblasts elicited extracellular signal-regulated kinase (Erk) signaling, which w...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1132
更新日期:2004-12-01 00:00:00
abstract::The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the inte...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2960
更新日期:2014-10-01 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::Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune syste...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1519
更新日期:2007-11-01 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 lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1506
更新日期:2007-10-01 00:00:00
abstract::The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2064
更新日期:2011-07-03 00:00:00
abstract::Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0385-2
更新日期:2019-06-01 00:00:00