Abstract:
:Regulatory T cells (T(reg) cells) develop from progenitor thymocytes after the engagement of T cell antigen receptors (TCRs) with high-affinity ligands, but the underlying molecular mechanisms are still unclear. Here we show that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR stimulation in thymocytes, have essential roles in T(reg) cell development. Mice that lacked all Nr4a factors could not produce T(reg) cells and died early owing to systemic autoimmunity. Nr4a receptors directly activated the promoter of the gene encoding the transcription factor Foxp3, and forced activation of Nr4a receptors bypassed low-strength TCR signaling to drive the T(reg) cell developmental program. Our results suggest that Nr4a receptors have key roles in determining CD4(+) T cell fates in the thymus and thus contribute to immune homeostasis.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Sekiya T,Kashiwagi I,Yoshida R,Fukaya T,Morita R,Kimura A,Ichinose H,Metzger D,Chambon P,Yoshimura Adoi
10.1038/ni.2520subject
Has Abstractpub_date
2013-03-01 00:00:00pages
230-7issue
3eissn
1529-2908issn
1529-2916pii
ni.2520journal_volume
14pub_type
杂志文章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::Immune synapses form between T cells and antigen-presenting cells (APCs). Increasing evidence suggests synapses must form flexibly to accommodate ongoing motility and displacement of the synapse. Here, time-lapse total internal reflection fluorescence (TIRF) microscopy showed that signaling via the T cell antigen rece...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2364
更新日期:2012-07-01 00:00:00
abstract::The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream'...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1635
更新日期:2008-08-01 00:00:00
abstract::Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-alpha (STAT1-alpha) for signal tra...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1025
更新日期:2004-02-01 00:00:00
abstract::DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1204
更新日期:2005-06-01 00:00:00
abstract::In recent years, a population of unconventional T cells called 'mucosal-associated invariant T cells' (MAIT cells) has captured the attention of immunologists and clinicians due to their abundance in humans, their involvement in a broad range of infectious and non-infectious diseases and their unusual specificity for ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/s41590-019-0444-8
更新日期:2019-09-01 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::Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-transl...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3487
更新日期:2016-08-01 00:00:00
abstract::Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death dom...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni0503-410
更新日期:2003-05-01 00:00:00
abstract::Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(α)14-J(α)18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2051
更新日期:2011-06-12 00:00:00
abstract::Members of the Toll-like receptor (TLR) family are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated by comparison of the incidence of disease among people having different polymorphisms in genes that participate in TLR signaling. These st...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1116
更新日期:2004-10-01 00:00:00
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...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2284
更新日期:2012-05-18 00:00:00
abstract::Myelin basic protein-specific CD8(+) T cells can induce central nervous system autoimmunity; however, immune tolerance prevents these autoreactive cells from causing disease. To define the mechanisms that mediate tolerance, we developed two T cell receptor-transgenic mouse lines with different affinities for the H-2K(...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1073
更新日期:2004-06-01 00:00:00
abstract::Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intra...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2573
更新日期:2013-06-01 00:00:00
abstract::EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is as...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/85266
更新日期:2001-03-01 00:00:00
abstract::In the version of this article initially published, the Supplementary Note was missing. The Supplementary Note has now been provided online and is cited in the Methods section of the article. The error has been corrected in the HTML and PDF version of the article. ...
journal_title:Nature immunology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41590-018-0104-4
更新日期:2018-06-01 00:00:00
abstract::Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional chemokine CXCL10. By extending those initial findings to pre-clinical mod...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0321-5
更新日期:2019-03-01 00:00:00
abstract::Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sen...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1574
更新日期:2008-04-01 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 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::Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3-/- mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni976
更新日期:2003-10-01 00:00:00
abstract::The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1957
更新日期:2010-12-01 00:00:00
abstract::Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2408
更新日期:2012-11-01 00:00:00
abstract::While a number of extrinsic factors are known to promote the survival of plasma cells (PCs), the signaling intermediates involved remain poorly characterized. Here we identified inducible nitric oxide synthase (iNOS) as an intermediate that supported the survival of PCs. PCs deficient in iNOS (Nos2(-/-) PCs) showed en...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2806
更新日期:2014-03-01 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::CD4(+) T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (T(H)1) or T(H)2 lineages and instead favor the idea of a d...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1254
更新日期:2005-11-01 00:00:00
abstract::CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation p...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni872
更新日期:2003-01-01 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::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::Nonmuscle myosin light-chain kinase (MYLK) mediates increased lung vascular endothelial permeability in lipopolysaccharide-induced lung inflammatory injury, the chief cause of the acute respiratory distress syndrome. In a lung injury model, we demonstrate here that MYLK was also essential for neutrophil transmigration...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1628
更新日期:2008-08-01 00:00:00