Interferon alpha signalling id needed for the induction of systemic lupus disease in a TLR-7 induced model.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022. SAIC-SAI-SAFIS; 2022

Sociedad Argentina de Inmunologia

Several studies have demonstrated that altered Toll-like receptor (TLR)signaling contributes to the initiation and/or exacerbation of Systemic LupusErythematosus (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-7 signaling strongly induces the production of IFN-, C57BL/6 mice and IFNAR knockout mice were treated topically into the skinwith Imiquimod 5%, 3 times weekly for 8 weeks. Serum anti-DNA, anti-histoneantibodies and spleen lymphocytes populations were analyzed by ELISA andimmunofluorescence cytometry respectively. Kidney infiltration was investigatedlooking for the presence of CD45 + leukocytes using immunofluorescencecytometry.B6 mice treated with Imiquimod (IMQ) developed higher spleen weight andcellularity when compared to untreated mice (p<0,05). Increased amounts ofCD69 + , CD44 hi T cells, Th1 and Th17 were observed in spleen of IMQ treatedmice when compared to untreated B6 mice (p<0,001). In addition, B6 treatedmice showed increased CD19 + counts with elevated levels of CD19 + CD11c + andCD19 + Tbet + aged-associated B cells. A significant increase in anti-dsDNA andanti-histone IgG antibodies was detected in serum samples at 4 weeks andcontinued to increase at 8 weeks of treatment (p<0.02).IMQ treatment in IFNAR knockout mice did not induced splenomegaly. Althoughincreased amounts CD69 + T cells and high levels of Th1 cells were observed,no significant differences were detected in CD44 hi , Th17, CD19 + andCD19 + CD11c + or CD19 + Tbet + subpopulations when compared to untreatedIFNAR KO mice. Serum samples were negative for the presence of auto-antibodies. Finally, when we looked for the presence of CD45 + cells in kidney,B6 but not IFNAR KO treated mice showed significant leukocyte infiltration (p<).Our data show that IFN- signaling protects mice from immune dysregulationand organ infiltration in a model of TLR-7 induced lupus.