共查询到20条相似文献,搜索用时 0 毫秒
1.
2.
Regulatory T (Treg) cells maintain peripheral tolerance and limit effector responses to prevent excessive immune-mediated tissue damage. However, recent research reveals that Treg cells also dampen the induction of immune responses and, thus, must be controlled to enable the effective protection against infections and cancer. Until now, this control of Treg-cell function has been believed to be by communication through cytokines or by stimulation through co-stimulatory molecules on antigen-presenting cells. However, new evidence has demonstrated that Treg cells can also sense pathogens directly through Toll-like receptors (TLRs) and, consequently, modify their behaviour. This review examines the ramifications of TLR engagement on Treg cells and conventional T cells, and discusses the potential role of TLRs on Treg cells and the consequences for disease therapy. 相似文献
3.
Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors 总被引:14,自引:0,他引:14
Ju W Morishita W Tsui J Gaietta G Deerinck TJ Adams SR Garner CC Tsien RY Ellisman MH Malenka RC 《Nature neuroscience》2004,7(3):244-253
Regulation of AMPA receptor (AMPAR) trafficking is important for neural plasticity. Here we examined the trafficking and synthesis of the GluR1 and GluR2 subunits using ReAsH-EDT(2) and FlAsH-EDT(2) staining. Activity blockade of rat cultured neurons increased dendritic GluR1, but not GluR2, levels. Examination of transected dendrites revealed that both AMPAR subunits were synthesized in dendrites and that activity blockade enhanced dendritic synthesis of GluR1 but not GluR2. In contrast, acute pharmacological manipulations increased dendritic synthesis of both subunits. AMPARs synthesized in dendrites were inserted into synaptic plasma membranes and, after activity blockade, the electrophysiological properties of native synaptic AMPARs changed in the manner predicted by the imaging experiments. In addition to providing a novel mechanism for synaptic modifications, these results point out the advantages of using FlAsH-EDT(2) and ReAsH-EDT(2) for studying the trafficking of newly synthesized proteins in local cellular compartments such as dendrites. 相似文献
4.
Shelke Vishwadeep Kale Ajinath Anders Hans-Joachim Gaikwad Anil Bhanudas 《Journal of molecular medicine (Berlin, Germany)》2022,100(7):1017-1026
Journal of Molecular Medicine - Kidney disease affects more than 10% of the worldwide population and causes significant morbidity and mortality. Epigenetic mechanisms such as DNA methylation,... 相似文献
5.
Zhiguo Xie Gan Huang Zhen Wang Shuoming Luo Peilin Zheng Zhiguang Zhou 《Journal of molecular medicine (Berlin, Germany)》2018,96(8):741-751
The immune system can be divided into adaptive immunity and innate immunity. Adaptive immunity has been confirmed to be involved in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, the role of innate immunity in T1D has only been studied recently. T1D is caused by selective autoimmune destruction of pancreatic islet β cells. A series of studies have suggested that TLRs play a critical role in the pathogenesis of T1D. Aberrant TLR signaling will change immune homeostasis and result in immunopathological conditions such as endotoxin shock and autoimmune responses. Thus, TLR signaling pathways are supposed to be strictly and finely regulated. Epigenetics has recently been proven to be a new regulator of TLR expression. DNA methylation, histone modification, and microRNAs are the three main epigenetic modifications. This review will mainly focus on these epigenetic mechanisms of regulation of TLRs and the role of TLRs in the pathogenesis of T1D. 相似文献
6.
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals. 相似文献
7.
Toll-like receptors and autoimmunity 总被引:2,自引:0,他引:2
The understanding of autoimmune diseases experienced an impressive boost since the Toll-like receptors (TLRs) have been identified as possible key players in autoimmune pathophysiology. Although these receptors recognize a variety of structures derived from viruses, bacteria and fungi leading to subsequent initiation of the relevant immune responses recent data support the idea that TLRs are crucial in the induction and perpetuation of certain autoimmune diseases, especially the systemic lupus erythematosus (SLE). In this review we will summarize recent data on involvement of TLRs in the development of autoimmune diseases. This review will focus on TLRs 7, 8 and 9 which were originally identified as receptors specific for bacterial and viral RNA/DNA, but more recent in vitro and in vivo studies have linked these receptors to the detection of host RNA, DNA, and RNA- or DNA-associated proteins in the context of autoimmunity. 相似文献
8.
The identification of Toll-like receptors (TLRs) as key patten-recognition receptors of innate immunity has opened inquiries
into previously unknown disease mechanisms. The ability of TLRs to detect a spectrum of pathogen-derived molecules defines
their importance in innate immunity and provides a mechanistic link between infection and disease. Atherosclerosis is a chronic
inflammatory disease where immune and metabolic factors interact to initiate and propagate arterial lesions. An understanding
of TLRs in atherosclerosis could clarify the etiology of this complex process. Furthermore, the existence of host-derived
endogenous TLR ligands may implicate TLR involvement in disease mechanisms beyond innate immunity, such as a role in homeostatic
mechanisms to resolve injury. Our current knowledge of TLRs in atherosclerosis is discussed in this review with emphasis on
experimental studies in atherosclerosis-susceptible mouse models. Highlights from studies of TLR involvement in other disease
processes have demonstrated that TLR-dependent mechanisms probably parallel those found in atherosclerosis, some of which
could be important in mitigating atherosclerotic injury. Finally, an appreciation of the pro- and anti-atherosclerotic mechanisms
of TLR activation over the entire lifetime of an organism will provide clues to the role of TLRs in both health and disease. 相似文献
9.
10.
11.
12.
13.
Farzaneh Rahmani 《Expert Review of Clinical Immunology》2016,12(12):1289-1298
Introduction: Expression of various Toll-like receptors (TLR) in keratinocytes (KCs) has offered new insights into the pathogenesis of psoriasis. When plasmacytoid dendritic cells (pDCs) are scarce in established psoriatic lesions, KCs take the responsibility to secrete IFN type 1 through TLR9 activation. Antagonists of TLR7 and TLR8 and anti-IL-12/IL-23 substances have shown promising results in treating psoriasis.
Areas covered: References in this study were extracted from Scopus, PubMed and Embase databases by the search term: (‘Toll-Like Receptors’ OR ‘TLR’) AND (‘Psoriasis’ OR ‘Arthritis, Psoriatic’ OR ‘PsA’).
Expert commentary: As the prevailing cell type, KCs play a major role in the maintenance of psoriatic lesions. By specific upregulation of IL-36 R, KCs can start the IL-23/IL-12 axis, leading to production of major culprits of psoriatic phenotype IL-17 and IL-22. Targeting IL-36 R could be considered as a new therapeutic target to eliminate cutaneous manifestations of psoriasis. 相似文献
14.
Toll-like receptors: networking for success 总被引:17,自引:0,他引:17
Underhill DM 《European journal of immunology》2003,33(7):1767-1775
The innate immune system is essential for host defense and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells such as macrophages and dendritic cells, diverse signaling pathways are activated that combine to define inflammatory responses that direct sterilization of the threat and/or orchestrate development of the adaptive immune response. Innate immune signaling must be carefully controlled, and regulation comes in part from interactions between activating and inhibiting signaling receptors. Toll-like receptors (TLR) have recently emerged as key receptors responsible for recognizing specific conserved components of microbes including lipopolysaccharides from Gram-negative bacteria, CpG DNA, and flagellin. Full activation of inflammatory responses by TLR may require the assembly of receptor signaling complexes including other transmembrane proteins that may influence signal transduction. In addition to TLR, many additional receptors participate in innate recognition of microbes, and recent studies demonstrate strong interactions between signaling through these receptors and signaling through TLR. Useful models for these interacting signaling pathways are now emerging and should pave the way for understanding the molecular mechanisms that drive the rich diversity of inflammatory responses. 相似文献
15.
Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity 总被引:2,自引:0,他引:2 下载免费PDF全文
The Toll-like receptor (TLR) family provide key components of mammalian immunity and are part of the earliest surveillance mechanisms responding to infection. Their activation triggers the innate immune response, and is crucial to the successful induction of Th1/Th2-phenotyped adaptive immunity. Innate immunity was long considered to be non-specific and somewhat simple compared to adaptive immunity, mediated via the engulfment and lysis of microbial pathogens by phagocytic cells such as macrophages and neutrophils, and involving no complex protein-protein interactions. The emergence of the TLR field has contributed to a revision of our understanding, and innate immunity is now viewed as a highly complex process, in line with adaptive immunity. This review will give a brief overview of our current knowledge of TLR biology, and will focus on TLRs as key components in complex networks that activate, integrate and select the appropriate innate and adaptive immune responses in the face of immunological danger. 相似文献
16.
17.
Micera A Stampachiacchiere B Aronni S dos Santos MS Lambiase A 《Current opinion in allergy and clinical immunology》2005,5(5):451-458
PURPOSE OF REVIEW: This review will describe the structure, expression/distribution and functional activity of Toll-like receptors, in particular in the ocular structures. It will also discuss innate and adaptive immune responses, by exploring the possible modulation/regulation of innate and adaptive immunity by Toll-like receptors, in view of recent findings observed in the ocular surface. RECENT FINDINGS: Current knowledge indicates that Toll-like receptors represent essential elements in host defence against pathogens, a prerequisite to the induction of adaptive immune responses. The expression/distribution of Toll-like receptors in the healthy eye highlights the possible function of Toll-like receptors in both innate and adaptive responses during pathological conditions of the ocular surface. SUMMARY: Recent findings have greatly increased the knowledge of the possible role of Toll-like receptors in innate and adaptive immune responses. Toll-like receptors seem to play different roles in a wide range of activities of the immune system, and might represent an exclusive link between innate and adaptive responses under pathological conditions. Recent studies in ophthalmology have highlighted the role of Toll-like receptors in infections (keratitis) as well as in allergic states of the ocular surface. This review thus describes the relationship between Toll-like receptors and the main immune/structural cells taking part in inflammatory disorders. Understanding the complex mechanisms underlying Toll-like receptor localization and function will provide additional data that might help devise novel therapeutic approaches involving Toll-like receptors and their agonists, in an attempt to modulate the biased immune system. 相似文献
18.
Severe sepsis and Toll-like receptors 总被引:1,自引:0,他引:1
Severe sepsis dominates the mortality of non-cardiac intensive care units. The ingenious Toll-like receptor (TLR) system can
recognise many infectious organisms through relatively few receptors to trigger pro-inflammatory and anti-inflammatory cytokine
release. Further complexity arises from positive and negative signalling feedback loops. Severe sepsis may be a consequence
of an inappropriately excessive response or inadequate endogenous negative feedback. Therapies targeting these pathways are
currently being evaluated. Alternatively, in clinical scenarios such as compensatory anti-inflammatory response syndrome,
chronic viral sepsis or inadequate vaccine function, TLR signalling may be inadequate. TLR agonists may augment the innate
response and are being investigated. 相似文献
19.
20.
在许多发达国家中,约75%-80% 的高血压患者有不同程度肥胖,65% -75%的原发性高血压患者同时合并有肥胖.随着社会的发展,中国的肥胖性高血压(obesity-related hypertension)患病率也在逐年上升[1-3].肥胖性高血压为多因疾病,对肥胖性高血压机制的相关研究已成为热点,其形成机制可能涉及胰岛素抵抗、血清脂联素、高瘦素血症、交感系统活化、肾素-血管紧张素系统(renin-angiotensin system, RAS)、凝血因子改变,炎症、内皮功能障碍等,但尚未达成广泛共识[4, 5].现在越来越多的研究表明,Toll样受体家族(Toll-like receptors,TLRs)与其形成密切相关.深入探讨此种受体的作用,将为肥胖性高血压的治疗提供新的思路. 相似文献