Abstract:
:The family of mammalian Nod-like receptors (NLRs) consists of critical intracellular immune proteins structurally related to plant resistance proteins. The NLRs NALP3 and IPAF, for example, can each form a multiprotein proinflammatory complex called the 'inflammasome', and mutations in the gene encoding Nod2, another NLR, are positively associated with Crohn disease. Here we show that many NLRs interacted with the ubiquitin ligase-associated protein SGT1 and heat-shock protein 90 (HSP90), both of which have plant orthologs essential for R-protein responses. 'Knockdown' of SGT1 by small interfering RNA or chemical inhibition of HSP90 abrogated inflammasome activity, and inhibition of HSP90 blocked Nod2-mediated activation of the transcription factor NF-kappaB and reduced NALP3-mediated gout-like inflammation in mice. Our data demonstrate a similarity in one type of innate immunity in plants and mammals that is consistent with convergent evolution of a shared mechanism.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Mayor A,Martinon F,De Smedt T,Pétrilli V,Tschopp Jdoi
10.1038/ni1459subject
Has Abstractpub_date
2007-05-01 00:00:00pages
497-503issue
5eissn
1529-2908issn
1529-2916pii
ni1459journal_volume
8pub_type
杂志文章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::Immune responses to microbial challenge in various tissues are not the same. Organ-specific immune responses are adapted to maintain organ physiology. ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni0107-3
更新日期:2007-01-01 00:00:00
abstract::Chemokines facilitate leukocyte migration and positioning as well as other processes such as angiogenesis and leukocyte degranulation. The burgeoning knowledge on chemokines and their receptors has influenced many aspects of immunology, in part because cell migration is intimately related to leukocyte function. This o...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/84298
更新日期:2001-02-01 00:00:00
abstract::Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant eng...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3770
更新日期:2017-08-01 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::Cell fate 'decisions' involving multipotential progenitors seem to be 'dictated' by threshold activities of lineage-determining transcription factors. Such 'decisions' are now shown to be reinforced by the induction of secondary transcription factors that act in concert with the primary regulators. ...
journal_title:Nature immunology
pub_type: 评论,新闻
doi:10.1038/ni0207-119
更新日期:2007-02-01 00:00:00
abstract::TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiq...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3588
更新日期:2016-12-01 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
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::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::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...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2520
更新日期:2013-03-01 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/s41590-019-0476-0
更新日期:2019-10-01 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::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::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::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::We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of ma...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1001-962
更新日期:2001-10-01 00:00:00
abstract::Natural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface mol...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3437
更新日期:2016-06-01 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::Current approaches for the treatment of obesity, including diet and lifestyle changes, have not been successful in curtailing the obesity epidemic. The higher incidence of inflammation-associated chronic disease and greater susceptibility to infection in obese people represents a growing health threat. Improved unders...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2343
更新日期:2012-07-19 00:00:00
abstract::Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced brea...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.3691
更新日期:2017-03-22 00:00:00
abstract::Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in I...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2187
更新日期:2011-11-20 00:00:00
abstract::Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for lipopolysaccharide-induced activation of p38 but not of Jnk or...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1200
更新日期:2005-06-01 00:00:00
abstract::Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs. The Itch-Cyld complex sequentially cleaved Lys63-linked ubiquitin chains and...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2157
更新日期:2011-11-06 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::Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokin...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/90675
更新日期:2001-08-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathologic conditions ranging from cancer to obesity. These cells represent a pathologic state of activation of monocytes and relatively immature neutrophils. MDSCs are characterized by a distinct set of ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/s41590-017-0022-x
更新日期:2018-02-01 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::Oxidants such as H2O2 are connected to lymphocyte activation, but the molecular mechanisms behind this phenomenon are less clear. Here, I review data suggesting that by inhibiting protein tyrosine phosphatases, H2O2 plays an important role as a secondary messenger in the initiation and amplification of signaling at th...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1202-1129
更新日期:2002-12-01 00:00:00
abstract::The importance of protein glycosylation in the migration of immune cells throughout the body has been extensively appreciated. However, our awareness of the impact of glycosylation on the regulation of innate and adaptive immune responses is relatively new. An increasing number of studies reveal the relevance of glyco...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.f.203
更新日期:2008-06-01 00:00:00