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Critical role of Toll-like receptor 7 in Systemic Lupus Erythematosus

Defense Thèse de privat-docent : Univ. Genève, 2014
Abstract Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease associated with hormonal, environmental and genetic factors and characterized by the presence of circulating autoantibodies targeting self nucleic acids. Endosomal Toll-like receptors (eTLRs) such as TLR7, 8 and 9, are innate receptors that recognize foreign nucleic acids in order to eliminate pathogens. Overreaction of the immune system, as observed during SLE, leads to the recognition of self-DNA and self-RNA by eTLRs conducting to chronic inflammation and sustaining autoreactivity. In view of the possible role of TLR7 and TLR9 in the activation of dendritic cells and autoreactive B cells through RNA- or DNA-related immune complexes, we have explored their implication in murine SLE by introducing the Tlr7, Tlr8 and/or Tlr9 null mutations into lupus-prone mice and followed the autoimmune features. Accumulating evidence supports the idea that TLR7 and TLR9 play important but distinct roles in the development of autoimmune responses in SLE. In our different works compiled in this thesis we show that enhanced TLR7 activity is critical for the accelerated development of SLE in lupus-prone mice and pointed out the complex interplay between endosomal receptors. TLR7 has shown to be a valuable target for therapeutic approaches in autoimmunity such as SLE.
Keywords Systemic Lupus erythematosus-TLR7-TLR9-TLR8-Autoantibody
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Research group Groupe Santiago-Raber Marie-Laure (pathologie et immunologie) (915)
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SANTIAGO-RABER, Marie-Laure. Critical role of Toll-like receptor 7 in Systemic Lupus Erythematosus. Université de Genève. Thèse de privat-docent, 2014. doi: 10.13097/archive-ouverte/unige:46316 https://archive-ouverte.unige.ch/unige:46316

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Deposited on : 2015-02-04

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