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TLR7 and TLR9 in SLE: when sensing self goes wrong

  • Singapore Immunology Network
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Abstract

Autoreactive B and T cells are present in healthy, autoimmunity-free individuals, but they are kept in check by various regulatory mechanisms. In systemic lupus erythematosus (SLE) patients, however, autoreactive cells are expanded, activated, and produce large quantities of autoantibodies, directed especially against nuclear antigens. These antibodies form immune complexes with self-nucleic acids present in SLE serum. Since self-DNA and self-RNA in the form of protein complexes can act as TLR9 and TLR7 ligands, respectively, TLR stimulation is suggested as an additional signal contributing to activation and/or modulation of the aberrant adaptive immune response. Data from mouse models suggest a pathogenic role for TLR7 and a protective role for TLR9 in the pathogenesis of SLE. Future investigations are needed to elucidate the underlying modulatory mechanisms and the role of TLR7 and TLR9 in the complex pathogenesis of human SLE.

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Celhar, T., Magalhães, R. & Fairhurst, AM. TLR7 and TLR9 in SLE: when sensing self goes wrong. Immunol Res 53, 58–77 (2012). https://doi.org/10.1007/s12026-012-8270-1

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