Anti-IL9 Therapy in a Murine Model of Systemic Lupus Erythematosus (SLE) 9226

Abstract Description Systemic lupus erythematosus (SLE) is an antibody-mediated autoimmune disease characterized by systemic immune complex deposition with widespread effects on the skin, joints, kidneys, and brain. In patients, SLE is often diagnosed via antinuclear antibodies, most reliably anti-ds DNA antibody (Ab). Patients with SLE have been shown to have elevated IL-9 protein and mRNA compared to healthy controls. While there is no murine model that completely recapitulates human SLE, the standard MRL/lpr model rapidly manifests several aspects of this heterogeneous disease. We subcutaneously injected anti-IL9 or isotype control Ab every week into female MRL/lpr mice for up to 20 weeks. We performed serial saphenous vein bleeds and performed enzyme linked immunosorbent assays (ELISA) to measure anti-ds DNA Abs. At 20 weeks, the mice were euthanized, and flow cytometry assays were performed on the spleen and inguinal lymph node (iLN) to assess the expansion of the germinal center (GC) B cells and T follicular helper (Tfh) cells. We observed a significant increase in the GC B cell and the Tfh population in the anti-IL9 treated compared to isotype control-treated mice. We also observed a significant increase in the level of anti-ds DNA Ab in the anti-IL9 treated compared to the isotype control. The increase in GC B cell expansion and Tfh expansion as well as the increase in anti-ds DNA Ab in the anti-IL9 treatment group suggests that IL-9 may play a protective role in this model. Funding Sources Supported by grants from NIH T32 HL007910 and R01 AI180518. Topic Categories Basic Autoimmunity (BA)