Background Leukocyte immunoglobulin-like receptor A3 (LILRA3) is the soluble protein of LILRs family. LILRA3 exhibits a 6.7-kb deletion variation among individuals. The deletion removes all of four Ig-like domains, resulting in a ‘non-functional LILRA3’. Our research group identified the functional LILRA3 as a novel genetic risk for systemic lupus erythematosus. The aim of this study was to functionally characterize the impact of LILRA3 in the pathogenesis of SLE.
Methods We constructed a humanized LILRA3 knock-in (LILRA3-KI) mouse in C57BL/6 (B6) mice background. The lupus-like disease was induced by repeated epicutaneous stimulation with Toll-like receptor (TLR)-7 agonist imiquimod (IMQ) on both ears of mice. All of the mice were euthanized four weeks after the initiation of treatment. The spleen and serum samples were collected. Immunocyte populations were determined by staining with fluorescently-conjugated antibodies and analysed by flow cytometry. Serum antibodies were detected by enzyme-linked immunosorbent assay (ELISA).
Results The mice developed lupus-like disease following 4 weeks of treatment with imiquimod. LILRA3-KI mice exposed to imiquimod showed increased innate and adaptive immune response, including splenomegaly (p < 0.05) and elevated levels of serum anti-dsDNA IgG (p < 0.05), compared to WT mice. The frequencies of M1 macrophage, M2 macrophage, T follicular helper cells (Tfh), germinal center (GC) B, and plasma B cells were increased in KI mice (p < 0.05).
Conclusions Our data demonstrated that LILRA3 promoted the TLR7-driven lupus autoimmunity with the excessive expansion of macrophages, Tfh, GC B, and plasma B cells.
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