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See Accompanying Article (see + accompanying_article)
Selected AbstractsMolecular mimicry in innate immunity?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008The viral RNA recognition receptor TLR7 accelerates murine lupus Abstract Toll-like receptors (TLR), such as TLR7, were first described as innate pathogen recognition receptors that trigger appropriate antimircrobial immune responses upon exposure to pathogen-associated molecules, e.g. viral ssRNA. In parallel to ongoing studies on TLR-biology, mounting experimental evidence suggests that endogenous RNA-related autoantigens may also activate dendritic cells (DC) and B cells through TLR7. TLR7-mediated DC activation, autoantibody secretion, lymphoproliferation, and autoimmune tissue injury, are frequently observed in various murine models of systemic lupus and lupus nephritis. A paper in the current issue of the European Journal of Immunology, provide striking experimental evidence for this concept; the authors show that the Y chromosome-linked autoimmune accelerating (Yaa) translocation from the X-chromosome, consisting of 16 genes including Tlr7, largely mediates the autoimmune phenotype via the duplication of Tlr7. This finding highlights the need to address the significance of TLR7 in human lupus in terms of both genetic risk and as a therapeutic option. See accompanying article: http://dx.doi.org/10.1002/eji.200838138 [source] Slamming the DOR on chemokine receptor signaling: Heterodimerization silences ligand-occupied CXCR4 and ,-opioid receptorsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Dale Hereld Abstract Dimerization has emerged as a common mechanism for regulating the function of G protein-coupled receptors (GPCR). Among these are chemokine receptors, which detect various chemokines and regulate a range of physiological process, including immune cell trafficking, cancer cell migration, and neuronal patterning. Homo- and heterodimerization in response to chemokine binding has been shown to be required for the initiation or alteration of signaling by a number of chemokine receptors. In this issue of the European Journal of Immunology, a new study indicates that the formation of heterodimers of chemokine receptor CXCR4 and the ,-opioid receptor (DOR) prevents each of them from actively signaling, suggesting a novel mechanism for silencing GPCR function. See accompanying article: http://dx.doi.org/10.1002/eji200737630 [source] Osteopontin as a new player in mast cell biologyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Silvia Bulfone-Paus Abstract The secreted glycoprotein osteopontin (OPN) sets into motion an astounding variety of activities that range from bone remodeling via immunomodulation to the inhibition of apoptosis. In the current issue of the European Journal of Immunology, OPN now also enters mast cell biology and the regulation of IgE-dependent immune responses since it is reported that connective tissue-type mast cells from fetal murine skin constitutively secrete biologically active OPN. Moreover, it is shown that, in vitro, OPN augments IgE-mediated mast cell degranulation and migration via ligand binding to cognate OPN receptors on the mast cell surface (CD44, ,v integrin) and that the magnitude of an IgE-mediated passive cutaneous anaphylaxis reaction is augmented by OPN in vivo. Here, we discuss why this newly discovered property of OPN fits well into the emerging concept that OPN may serve as a multi-purpose environmental damage-response protein. See accompanying article: http://dx.doi.org/10.1002/eji200737057 [source] Back to the beginning , the quest for thymic epithelial stem cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Jeremy B. Swann Abstract Stem cell-based therapies hold much promise for the rejuvenation of aged or damaged tissues; however, before such cells can be used therapeutically, they must first be accurately identified. In this issue of the European Journal of Immunology it is reported that MTS24, a marker previously associated with progenitor cells of the thymic epithelium, fails to accurately identify epithelial cell populations with the ability to reconstitute a functional thymus. This finding demonstrates that much progress needs to be made before thymic epithelial stem cells can be harnessed for clinical benefit. See accompanying article: http://dx.doi.org/10.1002/eji.200737275 [source] Staying alive , naïve CD4+ T cell homeostasisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Jared F. Purton Abstract The immune system must maintain a broad repertoire of naïve T cells in order to respond to the diverse range of pathogens that it will encounter over the course of a lifetime. Although it is known that contact with IL-7 is crucial for the survival of naïve T cells, the precise intracellular signals that mediate its effects remain obscure. An article in this issue of the European Journal of Immunology has found that IL-7 requires the coordinated action of multiple pathways to maintain naïve CD4+ T cells. See accompanying article: http://dx.doi.org/10.1002/eji.200737234 [source] Genomic variants of TLR1 , It takes (TLR-)two to tangoEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Abstract Toll-like receptors (TLR) are innate immune sensors of microbial cell wall products that initiate early host responses. The TLR2 receptor complex has been shown to contain heterodimers of TLR2 with either TLR1 or TLR6 enabling the host to detect different microbial molecules, such as lipopeptides of different chemical composition. In this issue of the European Journal of Immunology, an important role in the sensing of microbial products for I602S, a single nucleotide polymorphism (SNP) in human TLR1 has been identified. This result, in combination with another recently published report on this polymorphism elucidating a functional role in cell trafficking (surface expression of the receptor complex in individuals carrying the SNP was altered), provide genetic evidence affirming the important function of TLR1 as an essential co-receptor for TLR2. See accompanying article: http://dx.doi.org/10.1002/eji200737034 [source] MR1-restricted V,19i T cells , a second population recognizing lipid antigens?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Jens Schümann Abstract There is increasing evidence that T cells recognizing lipid antigens contribute to the immunological regulation of different disease conditions including autoimmunity. The best-known subset is CD1d-restricted lipid-reactive T cells characterized by the expression of an invariant TCR, chain. Much less is known about the biology of another invariant T cell subset, which is restricted to the MHC class I-like molecule MR1. A beneficial role of MR1-restricted T cells has been suggested in a mouse EAE model. However, the nature of antigens that can be presented by MR1 to this invariant T cell subset remained largely unclear. An article in this issue of the European Journal of Immunology presents strong indications that derivatives of ,-mannosyl ceramide (,-ManCer), i.e. glycolipids, can serve as ligands for MR1-restricted invariant T cells. In addition to that, the structure of the ,-ManCer sphingosine chain influences the Th1-Th2 polarization of the cytokine response. These important new findings will foster further research on the identity of physiological ligands for MR1-restricted T cells and on their relation with immunoregulation. See accompanying article: http://dx.doi.org/10.1002/eji.200636689 [source] Immune modulation of HLA-G dimer in maternal-fetal interfaceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Kimiko Kuroki Abstract HLA-G is a non-classical human MHC class I molecule, which has several characteristics distinct from classical MHC, such as low polymorphism and restricted tissue distribution. HLA-G is expressed on placenta, thymus and some tumors. At the maternal-fetal interface, trophoblasts do not express major classical MHC class I molecules (MHCI), HLA-A and -B, to prevent normal T cell responses. Instead, HLA-G is expressed and can suppress a wide range of immune responses by binding to inhibitory immune cell surface receptors, such as leukocyte Ig-like receptor (LILR) B1 and LILRB2. HLA-G exists in various forms, including ,2m-associated or -free disulfide-linked dimers that can be expressed either at the cell surface or in soluble form. However, until recently the physiological role of these different molecular forms has been unclear. In this issue of the European Journal of Immunology, one article demonstrates that the disulfide-linked homodimer of ,2m-associated HLA-G is the major fraction expressed by trophoblast cells. The HLA-G dimer modulates the function of LILRB1-expressing antigen-presenting cells by principally binding to LILRB1. On the other hand, another recent report showed that ,2m-free disulfide-linked HLA-G dimers are produced by villous cytotrophoblast cells. Taken together, these results provide strong evidence in support of the hypothesis that HLA-G dimers play a role in immune suppression at the maternal-fetal interface. Further in-depth investigation will help to clarify the precise mechanism of HLA-G receptor recognition and signaling in vivo and the role of these interactions in successful reproduction. See accompanying article: http://dx.doi.org/10.1002/eji.200737089 [source] Helminths, allergic disorders and IgE-mediated immune responses: Where do we stand?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Klaus Abstract Th2 responses induced by allergens or helminths share many common features. However, allergen-specific IgE can almost always be detected in atopic patients, whereas helminth-specific IgE is often not detectable and anaphylaxis often occurs in atopy but not helminth infections. This may be due to T regulatory responses induced by the helminths or the lack of helminth-specific IgE. Alternatively non-specific IgE induced by the helminths may protect from mast cell or basophil degranulation by saturating IgE binding sites. Both of these mechanisms have been implicated to be involved in helminth-induced protection from allergic responses. An article in the current issue of the European Journal of Immunology describes the generation of an anti- Nippostrongylus brasiliensis -specific IgE antibody which was used to identify a novel N. brasiliensis antigen (Nb-Ag1). The authors demonstrated that Nb-Ag1 specific IgE could only be detected for a short period of time during infection, and that these levels were sufficient to prime mast cells thereby leading to active cutaneous anaphylaxis after the application of Nb-Ag1. This is the first report clearly showing that a low level of helminth-specific IgE, transiently produced, is able to induce mast cell degranulation in the presence of large amounts of polyclonal IgE. See accompanying article: http://dx.doi/10.1002/eji.200737135 [source] Fine-tuning CD4+ central memory T cell heterogeneity by strength of stimulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Vandana Kalia Abstract The memory T cell pool serves as a relatively long-lived heterogeneous repository of antigen-experienced T cells that "remember" previous encounters with antigen. While heterogeneity in the memory T cell pool is now well established, signals regulating the generation of this memory T cell heterogeneity are not fully understood. Two articles in this issue of the European Journal of Immunology highlight the importance of the strength of antigenic stimulation in regulating the generation of phenotypically and functionally distinct CD4+ T cell memory subsets. New insights are also provided into key molecular players that likely mediate differences in homeostatic and secondary expansion between the memory subsets. See accompanying articles: http://dx.doi.org/10.1002/eji200737611 and http://dx.doi.org/10.1002/eji200737852 [source] Anti-cytokine vaccines and the immunotherapy of autoimmune diseasesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2006David Abstract Three papers in this issue of the European Journal of Immunology describe the use of cytokine vaccines to prevent autoimmune disease in experimental animals. The vaccines are based on interleukin 17 (IL-17), a cytokine that has recently been shown to play a central role in inflammation. See accompanying articles: http://dx.doi.org/10.1002/eji.200636484; http://dx.doi.org/10.1002/eji.200636658; http://dx.doi.org/10.1002/eji.200636662 [source] Scleroderma: it has been a long hard journeyINTERNAL MEDICINE JOURNAL, Issue 8 2006P. J. Roberts-Thomson Abstract Progress in the understanding of the aetiopathogenesis of scleroderma (systemic sclerosis) has been painfully slow and this has greatly impeded the application of specific disease modifying treatments. This article provides a brief historical overview of scleroderma (including the important Australian contribution of Dr Alfred Barnett and colleagues , see accompanying article in this issue on pages 513,18), highlights some recent pathogenic developments and summarises some exciting new therapies. Cautious optimism can now be offered to scleroderma sufferers. [source] | ||||||||||