Abstract:
:Toll-like receptor 3 (TLR3) recognizes double-stranded RNA and transmits signals to activate NF-kappaB and the interferon (IFN)-beta promoter via the newly identified adaptor, TICAM-1. The extracellular LRR domain of TLR3 is engaged in the ligand recognition, while the intracellular TIR domain is crucial for the adaptor binding and signal transduction upon ligand stimulation. Here, we analyzed TLR3 localization in human monocyte-derived immature dendritic cells (iDCs) and stable transfectants expressing human TLR3 by immunofluorescence staining and confocal microscopy. TLR3 was predominantly localized in specific but as yet unidentified intracellular vesicles where TLR3 signaling was initiated. Expression analysis of TLR3-tail-truncated mutants revealed that the cytoplasmic 'linker' region (residues 730-755) determines the intracellular localization of TLR3. Site-directed mutagenesis of the linker region allowed us to identify the relevant determinants as Arg(740) and Val(741) residues for intracellular expression of TLR3. Furthermore, alanine scanning of the linker region demonstrated that the Phe(732), Leu(742) and Gly(743) in the TLR3 cytoplasmic linker region are essential for ligand-induced NF-kappaB and IFN-beta promoter activation. Thus, the cytoplasmic linker region of TLR3 regulates receptor retention inside the organelle and signaling, which may be closely linked to TLR3 function in DCs.
journal_name
Int Immunoljournal_title
International immunologyauthors
Funami K,Matsumoto M,Oshiumi H,Akazawa T,Yamamoto A,Seya Tdoi
10.1093/intimm/dxh115subject
Has Abstractpub_date
2004-08-01 00:00:00pages
1143-54issue
8eissn
0953-8178issn
1460-2377pii
dxh115journal_volume
16pub_type
杂志文章abstract::HIV infected T and monocytic cell lines could activate and fix C3 fragments when incubated in human serum under conditions allowing for activation of the alternative complement pathway. Normal T lymphocytes incubated with HIV could also activate and fix C3. This activity was, at least in part, the property of the viru...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.4.395
更新日期:1991-04-01 00:00:00
abstract::Dendritic cells (DC) sense saprophytic yeast and pathogenic, filamentous forms of Candida albicans in a specific way, resulting in disparate patterns of DC and T(h) cell activation. Using human and murine DC, such disparate patterns could be traced to the exploitation of distinct recognition receptors. Although usage ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh012
更新日期:2004-01-01 00:00:00
abstract::Peptide-MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activatio...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxt066
更新日期:2014-05-01 00:00:00
abstract::Non-obese diabetic (NOD) mice that are genetically deficient in either IFN-gamma or beta chain of the IFN-gammaR develop diabetes with similar kinetics to wild-type NOD mice. In the current study, we demonstrated that treatment of IFN-gamma signaling-deficient NOD mice with cyclophosphamide (CY) not only fails to indu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn080
更新日期:2008-09-01 00:00:00
abstract::It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal ente...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg080
更新日期:2003-07-01 00:00:00
abstract::O-acetyl GD3 ganglioside is a cell surface molecule of some neural, neural crest and renal cells. Here we show, by using mAbs specific for O-acetyl GD3 (clone 27A) and flow-cytometric, biochemical or immunological techniques, that it is also expressed at high intensity level on the surface of 49.6% (median) of the CD3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.9.1409
更新日期:1994-09-01 00:00:00
abstract::Impaired lymphocyte function is a common feature of human diabetes. Nucleoside transport across the plasma membrane is an essential step during lymphocyte growth and activation. In our study, we evaluated the impact of diabetic conditions on nucleoside transport system in B lymphocytes. Examination of the nucleoside t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh195
更新日期:2005-02-01 00:00:00
abstract::Src homology region 2-domain-containing phosphatase-1 (SHP-1) plays an important role in the regulation of signaling from various receptors in hematopoietic cells. In mast cells, SHP-1 has been shown to negatively regulate the initial signaling triggered by high-affinity receptor for IgE (FcepsilonRI) and positively r...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm070
更新日期:2007-09-01 00:00:00
abstract::Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.7.1075
更新日期:1999-07-01 00:00:00
abstract::Peyer's patch (PP) organogenesis proceeds through three histologically distinct steps: formation of organizing centers expressing VCAM-1 and ICAM-1 in segregated regions of the intestine at 15.5 days post-coitus (d.p.c.) (step I), accumulation of blood cells expressing different sets of surface markers to this region ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.643
更新日期:1999-05-01 00:00:00
abstract::In this study, we analyzed peripheral blood CD4+CD8+ double-positive (DP) lymphocytes in adult cynomolgus monkeys (Macaca fascicularis). Forty of 55 monkeys had > 5% of the peripheral blood DP subpopulation (9.3 +/- 5.9%; mean +/- SD) in peripheral blood lymphocytes (PBL) in contrast to a low percentage of peripheral ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.4.591
更新日期:1997-04-01 00:00:00
abstract::Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). She...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv067
更新日期:2016-04-01 00:00:00
abstract::The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC-peptide complexes). To examine this relationship, we employed target cell lysis as a quantitative measure and established a set of four CTL clones that ex...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.6.817
更新日期:2001-06-01 00:00:00
abstract::The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aqui...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.4.569
更新日期:1999-04-01 00:00:00
abstract::Human intestinal intraepithelial lymphocytes (iIEL) are a unique population of predominantly CD8 alpha beta+, TCR alpha beta+ lymphocytes and, to a lesser extent, TCP gamma delta+ lymphocytes that proliferate poorly to anti-CD3 mitogenic signals but display significant cytolytic activity. Studies in mouse model system...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/7.8.1237
更新日期:1995-08-01 00:00:00
abstract::We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile rate-limiting enzyme in the synthesis of polyamines thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.11.1777
更新日期:1994-11-01 00:00:00
abstract::Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulating effects in animal models, inhibiting toxic shock, progressive autoimmune disease and cancer. In humans, linomide strongly reduced the appearance of new lesions in multiple sclerosis yet enhanced immune responses after bone marrow transplantation. ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.10.1603
更新日期:1996-10-01 00:00:00
abstract::Although there has been extensive analysis on the capacity of MHC-peptide tetramers to bind antigen-specific TCR, there have been comparatively few studies regarding the role of the CD4 and CD8 co-receptors in binding and activation by these multimeric molecules. Here, we start from the observation that different anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/14.1.39
更新日期:2002-01-01 00:00:00
abstract::The two-signal model states that activation of naive T cells requires a signal 1 stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1 alone is sufficient for pre-activated T cells. Recently, however, it has been shown that under certain conditions T cells can bypass the requirement for co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.5.619
更新日期:1998-05-01 00:00:00
abstract::The human chymase (HC) is a major granule constituent of mast cells (MCs) residing in the connective tissue and the sub-mucosa. Although many potential substrates have been described for this important MC enzyme, its full range of in vivo substrates has most likely not yet been identified. A major step toward a better...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn128
更新日期:2009-01-01 00:00:00
abstract::Lymphocyte homing to lymph nodes is regulated by transient but specific interactions between lymphocytes and high endothelial venules (HEVs), the initial phase of which is mainly governed by the leukocyte adhesion molecule L-selectin, which recognizes sulfated and sialylated O-linked oligosaccharides displayed on sial...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh128
更新日期:2004-09-01 00:00:00
abstract::Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by a murine hybridoma, was originally found to inhibit the generation of lipopolysaccharide (LPS)-induced Ig-secreting cells. Most recently, we demonstrated the recombinant form of the ubiquitin-like segment (rUbi-L) or MNSF beta, an isoform of MN...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.11.1659
更新日期:1996-11-01 00:00:00
abstract::In vaccine development, a major objective is to induce strong, specific T cell responses. This might be obtained by targeting antigen to cell surface molecules that efficiently channel the antigen into endocytic compartments for loading of MHC molecules. Antibodies have been used to deliver antigen; however, it is imp...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf110
更新日期:2002-12-01 00:00:00
abstract::Interleukin 3 (IL-3) promotes the survival and proliferation of hematopoietic cells of various lineages in culture. Like most other hematopoietic colony stimulating factors, its mode of action is unknown. However, binding of the lymphokine induces protein tyrosine phosphorylation and enhanced glucose transport in some...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.8.827
更新日期:1991-08-01 00:00:00
abstract::The TCR is responsible for the specificity of cytotoxic T lymphocytes (CTL) by recognizing peptides presented in the context of MHC. By producing recombinant soluble TCR, it is possible to study this interaction at the molecular level. We generated single-chain TCR (scTCR) from tumor infiltrating lymphocytes (TIL) and...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.745
更新日期:1999-05-01 00:00:00
abstract::Previously we observed elevation of the serum concentration of two acute-phase protein (AFP) complement components (C9 and C1-inhibitor) in patients with chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non-responders (NR). In the present study we investigated the effect of high-dose IFN-alpha th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh024
更新日期:2004-01-01 00:00:00
abstract::Pathogenic intracellular bacteria often hijack macrophages for their propagation. The infected macrophages release IL-1β and IL-18 and simultaneously commit suicide, which is called pyroptosis; both responses require caspase-1. Here, we found that pyroptotic cells induced by microbial infection were efficiently engulf...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxs161
更新日期:2013-06-01 00:00:00
abstract::Analyses of bone marrow (BM) lymphocytes in C57BL/6 mice homozygous for the lpr mutation (B6.lpr) disclosed low numbers of pre-B and B cells, as compared with age-matched control B6 mice. BM depletion in B6.lpr mice was selective for B-lineage cells, appeared in young adults, and developed markedly with age and diseas...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.2.247
更新日期:1996-02-01 00:00:00
abstract::It is well established that the bacterial superantigens bind to both TCR beta-chain and, with moderate affinity, to MHC class II molecules. Class II-bearing cells bind the superantigen and present the superantigen to T cells expressing certain TCR beta-chain variable region alleles. We have observed that the superanti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.11.1721
更新日期:1995-11-01 00:00:00
abstract::The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point o...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.10.1349
更新日期:1993-10-01 00:00:00