The Experts below are selected from a list of 159990 Experts worldwide ranked by ideXlab platform
Hans-joachim Anders - One of the best experts on this subject based on the ideXlab platform.
-
Toll-Like Receptors in lupus nephritis.
Journal of biomedical science, 2018Co-Authors: Satish Kumar Devarapu, Hans-joachim AndersAbstract:The pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) is based on the loss of self-tolerance against ubiquitous autoantigens involving all mechanisms of adaptive immunity. However, data accumulating over the last decade imply an important role also for numerous elements of innate immunity, namely the Toll-Like Receptors in the pathogenesis of SLE. Here we discuss their role in the most common organ complication of SLE, i.e. lupus nephritis. We summarize experimental and clinical data on the expression and functional contribution of the Toll-Like Receptors in immune complex glomerulonephritis, and intrarenal inflammation. Based on these discoveries Toll-Like Receptors are evolving as therapeutic targets for the treatment of SLE and lupus nephritis.
-
Nucleic acids modulate autoimmunity through nucleic-acid-specific Toll-Like Receptors.
Current Medicinal Chemistry, 2006Co-Authors: Pandurang Shashikant Patole, Hans-joachim AndersAbstract:Autoimmune diseases are believed to develop mainly from three factors comprising genetic predisposition, environmental factors and immune (dys-) regulation. In this context, specific nucleic acids of exogenous or endogenous origin that signal through nucleic acid-specific Toll-Like Receptors (TLRs) have gained much research attention. During ongoing autoimmune disease microbial nucleic acids contribute to flares of disease and its aggravation leading to end organ damage, through unfavourable immune modulation. Apart from exogenous sources, nucleic acid molecules of endogenous origin emerge as potential ligands for Receptors of host defence, i.e. TLRs. Rapidly accumulating data on the role of nucleic acid-specific TLRs has not only provided insights about their pathogenic potential of endogenous nucleic acid molecules, but is also fuelling the development of novel immunotherapies.
Shizuo Akira - One of the best experts on this subject based on the ideXlab platform.
-
Toll-Like Receptors and innate immunity
Journal of Molecular Medicine, 2006Co-Authors: Satoshi Uematsu, Shizuo AkiraAbstract:The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by pattern recognition Receptors (PRRs), which recognize specific structures of microorganisms. Among them, Toll-Like Receptors (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa, and viruses, and play a major role in innate immunity. However, TLRs recognize pathogens either on the cell surface or in the lysosome/endosome compartment. Recently, cytoplasmic PRRs have been identified to detect pathogens that have invaded cytosols. In this review, we focus on the functions of PRRs in innate immunity and their downstream signaling cascades.
-
Toll-Like Receptors
Encyclopedia of Life Sciences, 2005Co-Authors: Tsuneyasu Kaisho, Shizuo AkiraAbstract:Toll-Like Receptors are mainly expressed on antigen-presenting cells and function as adjuvant Receptors. Their pleiotropic functions depend on a variety of signalling components. Keywords: Toll-Like Receptors; innate immunity; dendritic cells; interferon
-
Pathogen recognition with Toll-Like Receptors.
Current opinion in immunology, 2005Co-Authors: Taro Kawai, Shizuo AkiraAbstract:The innate immune system is an evolutionarily conserved system of defense against microbial infections. The family of Toll-Like Receptors is a major class of Receptors that sense molecular patterns associated with a broad range of pathogens including bacteria, viruses, fungi and protozoa. Following pathogen recognition, Toll-Like Receptors initiate intracellular signal transduction that results in the expression of genes involved in inflammation, antiviral responses and maturation of dendritic cells. Individual Toll-Like Receptors activate common and unique transcription factors through different signaling pathways to drive specific biological responses against microorganisms.
-
Microbial recognition by Toll-Like Receptors.
Journal of Dermatological Science, 2004Co-Authors: Kiyoshi Takeda, Shizuo AkiraAbstract:Toll-Like Receptors (TLRs) sense invasion of microorganisms by detecting microbial components that are conserved among pathogens. Recognition of microbial components by TLRs triggers activation of the innate immune system. Signaling pathways via TLRs originate from conserved cytoplasmic Toll/IL-1 receptor (TIR) domains. Recent accumulating evidence demonstrates that TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF, and TRAM, regulate TLR-mediated signaling pathways. MyD88 is common to all TLR-mediated pathways, which lead to the production of inflammatory cytokines, whereas TRIF mediates induction of IFN-β in TLR3 and TLR4 signaling pathways. TIRAP/Mal is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses.
-
Mammalian Toll-Like Receptors.
Current opinion in immunology, 2003Co-Authors: Shizuo AkiraAbstract:Toll-Like Receptors (TLRs) are essential in the host defense against microbial pathogens. Individual TLRs recognize distinct structural components of pathogens and evoke inflammatory responses. Recent evidence indicates that TLRs recognize not only bacteria and fungi but also viruses. The molecular mechanisms by which TLRs induce differential gene expression are now beginning to be clarified.
Ann Marshak-rothstein - One of the best experts on this subject based on the ideXlab platform.
-
Toll-Like Receptors in systemic autoimmune disease
Nature Reviews Immunology, 2006Co-Authors: Ann Marshak-rothsteinAbstract:Autoreactive B cells can be activated effectively in vitro by endogenous DNA or RNA, as well as by DNA- or RNA-binding proteins, through a mechanism that depends on the B-cell receptor and Toll-Like receptor 7 (TLR7) and/or TLR9. B-cell responses to RNA-associated autoantigens are markedly increased by type I interferons (IFNs). Similarly, it seems that TLR7 and TLR9 have important roles in the activation of plasmacytoid dendritic cells, through a mechanism that depends on the low-affinity receptor for IgG (FcγRIIa; also known as CD32), leading to the production of large amounts of type I IFNs. Mice that inherit the Y-chromosome-linked autoimmune accelerator ( Yaa ) mutation express twice the normal amount of TLR7 and are hyper-responsive to TLR7 ligands. The increased amount of TLR7 might account for the role of TLR7 in the acceleration of autoimmune disease in these mice. TLR9-deficient autoimmune-prone mice have a decreased capacity to produce antibodies specific for double-stranded DNA or nucleosomes, but they produce normal or increased amounts of antibodies specific for RNA-associated autoantigens. Nevertheless, TLR9 deficiency can lead to exacerbation of clinical disease in some animal models of systemic lupus erythematosus. TLR7-deficient autoimmune-prone mice have a decreased capacity to produce antibodies specific for RNA-associated autoantigens. In contrast to TLR9 deficiency, TLR7 deficiency does not lead to exacerbated clinical disease. In addition to DNA and RNA, other endogenous TLR ligands that are released from dead or dying cells or are released as a result of tissue injury have been found either to promote or to downregulate chronic inflammatory conditions. Toll-Like Receptors are well known as sensors of microorganisms, but they can also sense endogenous molecules. This article describes when this might occur and how it might activate autoreactive B cells and plasmacytoid dendritic cells in systemic autoimmune disease. Toll-Like Receptors (TLRs) have a crucial role in the early detection of pathogen-associated molecular patterns and the subsequent activation of the adaptive immune response. Whether TLRs also have an important role in the recognition of endogenous ligands has been more controversial. Numerous in vitro studies have documented activation of both autoreactive B cells and plasmacytoid dendritic cells by mammalian TLR ligands. The issue of whether these in vitro observations translate to an in vivo role for TLRs in either the initiation or the progression of systemic autoimmune disease is a subject of intense research; data are beginning to emerge showing that this is the case.
-
Toll-Like Receptors, endogenous ligands, and systemic autoimmune disease.
Immunological reviews, 2005Co-Authors: Ian R. Rifkin, Elizabeth A. Leadbetter, Liliana Busconi, Gregory A. Viglianti, Ann Marshak-rothsteinAbstract:The critical role of Toll-Like Receptors (TLRs) as mediators of pathogen recognition by the innate immune system is now firmly established. Such recognition results in the initiation of an inflammatory immune response and subsequent instruction of the adaptive immune system, both of which are designed to rid the host of the invading pathogen. More controversial is the potential role of TLRs in the recognition of endogenous ligands and what effect this might have on the consequent development of autoimmune or other chronic sterile inflammatory disorders. An increasing number of studies implicate TLRs as being involved in the immune response to self-molecules that have in some way been altered from their native state or accumulate in non-physiologic sites or amounts, although questions have been raised about possible contaminants in certain of these studies. In this review, we discuss the evidence for endogenous ligand-TLR interactions with particular emphasis on mammalian chromatin, systemic lupus erythematosus, and atherosclerosis. Overall, the data support the general concept of a role for TLRs in the recognition of endogenous ligands. However, the precise details of the interactions and the extent to which they may contribute to the pathogenesis of human disease remain to be clarified.
Marta Muzio - One of the best experts on this subject based on the ideXlab platform.
-
Toll-Like Receptors IN CHRONIC LYMPHOCYTIC LEUKEMIA
Mediterranean journal of hematology and infectious diseases, 2012Co-Authors: Marta Muzio, Eleonora Fonte, Federico Caligaris-cappioAbstract:Toll-Like Receptors belong to the pattern recognition Receptors family present on a variety of immune cells including normal and malignant B-cells. They act as immediate molecular sentinels of innate immunity but also act as a molecular bridge between the innate and the adaptive immune response; distinct Toll-Like Receptors are able to bind specific pattern molecules of bacteria, viruses and autoantigens. In this review we will briefly introduce the Toll-Like receptor family and their expression pattern, signaling and function in the B cell context; following we will summarize the published data on TLR in chronic lymphocytic leukemia, and we will discuss their emerging role in the modulation of leukemia pathobiology. Introduction. Inflammation primarily defends the host organism against infections and is a self limiting process; however, its deregulation leads to chronic inflammatory processes that may favor the
-
Toll-Like Receptors.
Microbes and infection, 2000Co-Authors: Marta Muzio, Alberto MantovaniAbstract:Toll-Like Receptors (TLRs) are a growing family of molecules involved in innate immunity. Accumulating evidence suggests that TLR molecules are involved in signalling receptor complexes which recognise components of Gram-positive and Gram-negative bacteria and mycobacteria. Differential expression and regulation as well as distinct though overlapping ligand recognition patterns may underlie the existence of a vast TLR family. Apparent structural and functional redundancy may render certain outputs of the TLR family robust.
A. Darise Farris - One of the best experts on this subject based on the ideXlab platform.
-
Toll-Like Receptors in Systemic Lupus Erythematosus: Potential Targets for Therapeutic Intervention
Current Allergy and Asthma Reports, 2012Co-Authors: Christopher G. Horton, A. Darise FarrisAbstract:Toll-Like Receptors (TLRs) have attracted increased attention in recent years, not only for their role in sensing conserved microbial components, but also in the realm of autoimmunity. Although TLRs are most widely known for their capacity to detect conserved motifs of infectious agents, mounting evidence indicates that these innate Receptors also promote autoimmune conditions by causing uncontrolled autoinflammation as a result of chronic recognition of self. In response to the need for modern approaches to treatment of autoimmune diseases, several groups have begun investigating ways to target TLRs as new therapeutic options for autoimmune conditions. Here we discuss recent data describing advances in TLRs as therapeutic targets for treatment of autoimmune diseases, with a focus on systemic lupus erythematosus.
