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  • Toll-like receptor 9 deficiency breaks tolerance to RNA - associated antigens and up-regulates Toll-like receptor 7 protein in Sle1 mice [Elektronski vir]
    Čelhar Kenanova, Teja ...
    Toll%like receptors (TLRs) 7 and 9 are important innate signaling molecules with opposing roles in the development and progression of systemic lupus erythematosus (SLE). While multiple studies ... support the notion of a dependency on TLR%7 for disease development, genetic ablation of TLR%9 results in severe disease with glomerulonephritis (GN) by a largely unknown mechanism. This study was undertaken to examine the suppressive role of TLR%9 in the development of severe lupus in a mouse model. Methods We crossed Sle1 lupus%prone mice with TLR%9%deficient mice to generate Sle1TLR%9%/% mice. Mice ages 4.5%6.5 months were evaluated for severe autoimmunity by assessing splenomegaly, GN, immune cell populations, autoantibody and total Ig profiles, kidney dendritic cell (DC) function, and TLR%7 protein expression. Mice ages 8%10 weeks were used for functional B cell studies, Ig profiling, and determination of TLR%7 expression. Results Sle1TLR%9%/% mice developed severe disease similar to TLR%9%deficient MRL and Nba2 models. Sle1TLR%9%/% mouse B cells produced more class%switched antibodies, and the autoantibody repertoire was skewed toward RNA%containing antigens. GN in these mice was associated with DC infiltration, and purified Sle1TLR%9%/% mouse renal DCs were more efficient at TLR%7%dependent antigen presentation and expressed higher levels of TLR%7 protein. Importantly, this increase in TLR%7 expression occurred prior to disease development, indicating a role in the initiation stages of tissue destruction. Conclusion The increase in TLR%7%reactive immune complexes, and the concomitant enhanced expression of their receptor, promotes inflammation and disease in Sle1TLR9%/% mice.
    Vir: Arthritis & rheumatology [Elektronski vir]. - ISSN 2326-5205 (Vol. 70, iss. 10, Oct. 2018, str. 1597-1609)
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2018
    Jezik - angleški
    COBISS.SI-ID - 4674673

    Povezava(-e):

    https://onlinelibrary.wiley.com/doi/10.1002/art.40535
    DOI

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