Accelerated model of lupus autoimmunity and vasculopathy driven by toll-like receptor 7/9 imbalance

Lupus Science & Medicine
Yudong LiuMariana J Kaplan

Abstract

Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background. Wild type (WT) and Tlr9-/- mice were epicutaneously treated with imiquimod cream 5% on both ears three times per week for indicated times. At euthanasia, mice were analysed for organ involvement, endothelium-dependent vasorelaxation, serum autoantibodies, and innate and adaptive immune responses. Compared with the lupus-like phenotype that develops in imiquimod-treated WT mice, Tlr9-/- mice exposed to imiquimod have increased severity of autoimmunity features and inflammatory phenotype that develops at earlier stages. These abnormalities are characterised by enhanced TLR7 expression and immune activation, increased immune complex deposition, Th1 T cells and dendritic cell kidney infiltration and significant ...Continue Reading

Citations

Sep 22, 2019·International Journal of Molecular Sciences·Bilikis Aderonke AbolarinwaYen-Hua Huang
Jan 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sathi Babu ChodisettiZiaur S M Rahman
Mar 24, 2020·International Reviews of Immunology·Alya HalkomQianjin Lu
Apr 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sathi Babu ChodisettiZiaur S M Rahman
Feb 1, 2020·Journal of Hypertension·Iñaki Robles-VeraMiguel Romero
May 21, 2019·Frontiers in Pharmacology·Jatin Sharma, Joseph Larkin
Apr 30, 2019·The Journal of Clinical Investigation·Jeeba KuriakoseHans Häcker
Jan 31, 2020·Frontiers in Immunology·Jena R WirthMelissa A Cunningham
Jul 22, 2020·Arthritis & Rheumatology·Xinghao WangMariana J Kaplan
Dec 19, 2020·Clinical and Experimental Immunology·A Paradowska-GoryckaM Olesińska
Oct 13, 2021·Science Signaling·Michiel van der VlistLinde Meyaard

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
transgenic
flow cytometry

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