MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression primarily at the post-transcriptional level. Emerging evidence supports a regulatory role for miRNAs in the immune response and autoimmunity. In this work, we investigated the implication of miR-21 in the experimentally inducible bm12→B6 cGVHD model of systemic lupus erythematosus (SLE). cGVHD host mice deficient in miR-21 show a 2-fold reduction in splenomegaly, significantly reduced autoantibody titers and down-regulated components of the CD40:CD40L and CD28:CD80/86 co-stimulation pathways. Furthermore, we demonstrate that miR-21-deficient hosts have reduced CD4(+) IL-17(+) cell populations and an expanded CD4(+) CD25(+) FoxP3(+) cell compartment. We propose that miR-21 has a pluripotent role, serving to link distinct lymphocyte signaling pathways and acting as a "rheostat" for signals that promote B and T cell activation in lupus. Collectively, our experiments demonstrate that miR-21 deficiency in cGVHD host mice is sufficient to protect from lupus-like autoimmunity.
Keywords: Autoantibodies; Autoimmunity; B cells; Co-stimulatory pathways; Cytokines; IL-17; Lupus; Lupus nephritis; MiR-21; MicroRNA; SLE; Splenomegaly; T cells; Th17; Tregs; cGVHD.
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