Journal
CLINICAL IMMUNOLOGY
Volume 162, Issue -, Pages 100-106Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.11.010
Keywords
SLE; Lupus; Autoimmunity; cGVHD; Autoantibodies; MicroRNA; MiR-21; Splenomegaly; T cells; B cells; Th17; Tregs; Co-stimulatory pathways; Cytoldnes; IL-17; Lupus nephritis
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Funding
- NIAMS NIH HHS [R03 AR060988, R21 AR063416] Funding Source: Medline
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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. (C) 2015 Elsevier Inc. All rights reserved.
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