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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02015

Lupus autoimmunity and metabolic parameters are exacerbated upon high fat diet-induced obesity due to TLR7 signalling

Noël Nanna Kazazian1,  Yawen Wang1,  Annie Roussel-Queval1, Laetitia Marcadet1, Lionel Chasson1,  Benoit Desnues1, Jonathan Charaix1,  Magali Irla1 and  Lena Alexopoulou1*
  • 1INSERM U1104 Centre d'immunologie de Marseille-Luminy, France

Systemic lupus erythematosus (SLE) patients have increased prevalence of metabolic syndrome but the underlying mechanisms are unknown. Toll-like receptor 7 (TLR7) that detects single stranded-RNA plays a key role in antimicrobial host defence and also contributes to the initiation and progression of SLE both in mice and humans. Here, we report the implication of TLR7 signalling in high fat diet (HFD)-induced metabolic syndrome and exacerbation of lupus autoimmunity in TLR8-deficient (TLR8ko) mice, which develop spontaneous lupus-like disease due to increased TLR7 signalling by dendritic cells (DCs). The aggravated SLE pathogenesis in HFD-fed TLR8ko mice was characterised by increased overall immune activation, anti-DNA autoantibody production, and IgG/IgM glomerular deposition that were coupled with increased kidney histopathology. Moreover, upon HFD TLR8ko mice developed metabolic abnormalities, including liver inflammation. In contrast, upon HFD TLR7/8ko mice did not develop SLE and both TLR7ko and TLR7/8ko mice were fully protected from metabolic abnormalities, including body weight gain, insulin resistance and liver inflammation. Interestingly, HFD led to an increase of TLR7 expression in WT mice, that was coupled with increased TNF production by DCs, and this phenotype was more profound in TLR8ko mice. Our study uncovers the implication of TLR7 signalling in the interconnection of SLE and metabolic abnormalities, indicating that TLR7 might be a novel approach as a tailored therapy in SLE and metabolic diseases.

Keywords: Toll-like receptor 7 (TLR7), Systemic lupus erythematosus (SLE, lupus), Obesity, Metabolic syndome, Innate immnuity, dendritc cells, animal model, Liver

Received: 15 Feb 2019; Accepted: 08 Aug 2019.

Copyright: © 2019 Nanna Kazazian, Wang, Roussel-Queval, Marcadet, Chasson, Desnues, Charaix, Irla and Alexopoulou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Lena Alexopoulou, INSERM U1104 Centre d'immunologie de Marseille-Luminy, Marseille, 13288, Provence-Alpes-Côte d'Azur, France,