INTERFERON ALPHA SIGNALING IS NEEDED FOR THE INDUCTION OF SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE IN A TLR-7 INDUCED MODEL

Mar del Plata

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2022; 2022

SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI)

Several studies have demonstrated that altered Toll-like receptor(TLR) signaling contributes to the initiation and/or exacerbation ofSystemic Lupus Erythematosus (SLE). In recent years, it has become apparent that TLR-7, which sense single-stranded RNA, contributes to the development of SLE. Taking into account that TLR-7signaling strongly induces the production of IFN-a, C57BL/6 miceand IFNAR knockout mice were treated topically into the skin withImiquimod 5%, 3 times weekly for 8 weeks. Serum anti-DNA, anti-histone antibodies and spleen lymphocytes populations were analyzed by ELISA and immunofluorescence cytometry respectively.Kidney infiltration was investigated looking for the presence of CD45+leukocytes using immunofluorescence cytometry. B6 mice treatedwith Imiquimod (IMQ) developed higher spleen weight and cellularitywhen compared to untreated mice(p<0,05). Increased amounts ofCD69+, CD44hi T cells, Th1 and Th17 were observed in spleen ofIMQ treated mice when compared to untreated B6 mice(p<0,04).In addition, B6 treated mice showed increased CD19+ counts withelevated levels of CD19+CD11c+ and CD19+Tbet+ aged-associatedB cells. A significant increase in anti-dsDNA and anti-histone IgG antibodies was detected in serum samples at 4 weeks and continuedto increase at 8 weeks of treatment(p<0.02).IMQ treatment in IFNAR knockout mice did not induced splenomegaly. Although increased amounts CD69+ T cells and high levels ofTh1 cells were observed, no significant differences were detected inCD44hi, Th17, CD19+ and CD19+CD11c+ or CD19+Tbet+ subpopulations when compared to untreated IFNAR KO mice. Serum sampleswere negative for the presence of auto-antibodies. Finally, when welooked for the presence of CD45+ cells in kidney, B6 but not IFNARKO treated mice showed significant leukocyte infiltration (p<0,05).Our data showed that disrupting IFN-a signaling protects mice fromimmune dysregulation and organ infiltration in a model of TLR-7 induced lupus.