Argyrios N Theofilopoulos

..Evidence, as reviewed here, strongly indicates that these sensors are primary contributors to autoimmune disease pathogenesis, spearheading efforts toward development of novel therapeutics for these disorders...

..These insights will permit the development of novel treatment modalities for these disorders...

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..These findings have resulted in a critical reappraisal of pathogenetic mechanisms, and provide a basis for the development of novel diagnostic and therapeutic modalities for these diseases...

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..Importantly, this helps provide an explanation for the high frequency of anti-nucleic acid Abs in lupus-like systemic autoimmunity...

..Our results demonstrate that Coronin-1A is required for the development of systemic lupus and identify actin-cytoskeleton regulatory proteins as potential targets for modulating autoimmune diseases...

..These findings strongly support the targeting of IFN-alphabeta in SLE and suggest that definition of the specific pathways critical for disease induction will be important for optimal intervention...

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..Thus, modulation of the cell cycle pathway may be a novel approach to reduce apoptosis-resistant pathogenic lymphocytes and to ameliorate systemic autoimmunity...

..Our findings identify a physiological role for Slfn2 in the defense against pathogens through the regulation of quiescence in T cells and monocytes...

..Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants...

..These findings establish the importance of Lbw2 in the BWF1 hybrid and indicate that Lbw2, by enhancing B cell hyperactivity, promotes the early polyclonal activation of B cells and subsequent production of autoantibodies...

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..Although this sensing is beneficial to the host, excessive activation and/or engagement by self molecules might induce autoimmune and other inflammatory disorders...

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..In its simplicity, this approach is likely to have application in humans, since it relies on conventional lymphopenia-inducing cancer therapies, infusion of autologous lymphocytes and, optimally, tumor-specific vaccination...

..The data indicate that type-I IFNs are important mediators in the pathogenesis of murine lupus, and that reducing their activity in the human counterpart may be beneficial...

..The results indicate that concomitant induction of the physiologic processes of homeostatic T cell proliferation and tumor antigen presentation in lymph nodes triggers a beneficial antitumor autoimmune response...

..Furthermore, we show that peripheral T(reg) cells are a dynamic population that may expand to limit immunopathology or promote chronic infection...

..We suggest that the paucity of autoreactive specificities created in the N region-lacking repertoire, and the resultant protection afforded to the newborn, may be the reason that TdT expression is delayed in ontogeny...

..The combined findings suggest that IFN-α/β receptor blockade, particularly when started at early disease stages, may be a useful treatment approach for human systemic lupus erythematosus and other autoimmune syndromes...

..Thus, gamma delta T cell homeostasis is maintained by trophic cytokines commonly used by other types of lymphoid cells, as well as by additional, as yet unidentified, gamma delta-specific factors...

..These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus...

..Thus, IRF8 and SLC15A4 may provide important targets for therapeutic intervention in human lupus...

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..Further work in defining methylation effects in the immune system is likely to lead to a more detailed understanding of the immune system and may point to the development of novel therapeutic approaches...

..A recent study in a diabetes-prone mouse model has provided strong evidence to support this hypothesis...

..Properties of HRG and possible protective actions of HRG-dependent clearance mechanisms are discussed...

..Mouse models of lupus should continue to serve as a vital approach to defining the genetics of SLE...

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..The SHP1-deficient phenotype is driven by microbes, which activate TLR signaling pathways to elicit IL-1 production. IL-1 signaling via MyD88 elicits inflammatory disease...

..The data suggest that transmethylation is required for CD4 T cell activation, and its inhibition may be a novel approach in the treatment of multiple sclerosis, and other CD4-mediated autoimmune diseases...

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..Defects in TCR signaling were associated with altered TCR zeta-chain phosphorylation...

..The findings indicate that HRG, by acting as a bridge between DNA on apoptotic cells and FcgammaRI on HMDM, is a key physiological mediator of apoptotic cell clearance by macrophages...

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..Furthermore, the close association of CD4(+) expansions with OB raises possibilities of development of novel diagnostic and therapeutic approaches...

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..Identification of the underlying genetic alteration responsible for this quantitative trait locus should provide new insights into lupus-modifying genes...

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..These findings have implications for the physiologic, pathological, and therapeutic regulation of costimulation...

..These studies will advance our knowledge of the mechanisms by which IFNs promote systemic autoimmunity and may contribute to the development of novel therapies for lupus and other autoimmune diseases. ..

..Findings generated from these studies, they expect, will significantly enhance efforts to define the etiopathogenesis of autoimmunity, and may lead to new approaches in the diagnosis and therapy of human SLE. ..

..These studies of cell cycle and apoptosis of aged T-cells will be instrumental to defining the molecular defects associated with immunologic senescence. ..

..Additional studies using reciprocal adoptive transfers will test the influence of environment on generation and survival of membory T cells. ..

..These results will further define the biology of homeostatic anti-self T cell proliferation, land may provide a new paradigm for understanding autoimmune syndromes, including lupus. ..

..Aside from providing a new mechanistic concept, blockade of these mediators may constitute a novel therapeutic approach for lupus and other autoimmune diseases. ..

..These studies will advance our knowledge of the mechanisms by which IFNs promote systemic autoimmunity and may contribute to the development of novel therapies for lupus and other autoimmune diseases. ..

..Aside from providing a new mechanistic concept, blockade of these mediators may constitute a novel therapeutic approach for lupus and other autoimmune diseases. ..

..These studies should yield significant new insights into the etiopathogenesis of systemic autoimmunity, and may lead to new diagnostic and therapeutic approaches for human SLE. ..

..These studies will advance our knowledge of the mechanisms by which IFNs promote systemic autoimmunity and may contribute to the development of novel therapies for lupus and other autoimmune diseases. ..

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..Identification of aberrancies in this central event is expected to have a significant impact on our ability to molecularly define autoimmune diseases and to devise specific and accurate means for their management...

..Creation of linkage maps and identification of pleotropic or specific autoimmune trait-associated genes will ultimately provide the means by which the molecular basis of lupus can be defined...

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