Sensors of the innate immune system: Their link to rheumatic diseases

Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nature Reviews Rheumatology (Impact Factor: 9.85). 02/2010; 6(3):146-56. DOI: 10.1038/nrrheum.2009.278
Source: PubMed


Evidence strongly suggests that excessive or protracted signaling, or both, by cell-surface or intracellular innate immune receptors is central to the pathogenesis of most autoimmune and autoinflammatory rheumatic diseases. The initiation of aberrant innate and adaptive immune responses in autoimmune diseases can be triggered by microbes and, at times, by endogenous molecules--particularly nucleic acids and related immune complexes--under sterile conditions. By contrast, most autoinflammatory syndromes are generally dependent on germline or de novo gene mutations that cause or facilitate inflammasome assembly. The consequent production of proinflammatory cytokines, principally interferon-alpha/beta and tumor necrosis factor in autoimmune diseases, and interleukin-1beta in autoinflammatory diseases, leads to the creation of autoamplification feedback loops and chronicity of these syndromes. 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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    Journal of Experimental Medicine 09/2014; 211(10). DOI:10.1084/jem.20132620 · 12.52 Impact Factor
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    • "Failure to distinguish foreign from host, however, can result in the development of autoimmune diseases, including organ-specific disease with restricted tissue involvement, such as multiple sclerosis and type I diabetes, or more systemic involvement such as systemic lupus erythematosus (SLE). For most idiopathic autoimmune diseases, components of both the innate and adaptive immune responses are needed [3-5]. To varying extents, environmental factors also contribute to the development of autoimmunity. "
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