title: MicroRNA-21 deficiency protects from lupus-like autoimmunity in the chronic graft-versus-host disease model of systemic lupus erythematosus.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Rheumatology, Sidney Kimmel Medical College, Thomas Jefferson University, 211 S. 9th St. Suite 210, Philadelphia, PA 19107, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Garchow
authors.affiliation: Department of Medicine, Division of Rheumatology, Sidney Kimmel Medical College, Thomas Jefferson University, 211 S. 9th St. Suite 210, Philadelphia, PA 19107, USA. Electronic address: marianthi.kiriakidou@jefferson.edu.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Kiriakidou
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000150:complications; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: Autoantibodies; Autoimmunity; B cells; Co-stimulatory pathways; Cytokines; IL-17; Lupus; Lupus nephritis; MiR-21; MicroRNA; SLE; Splenomegaly; T cells; Th17; Tregs; cGVHD