MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus.

Abstract

OBJECTIVE:

We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus.

MATERIALS AND METHODS:

Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry. Serum levels of anti-dsDNA, anti-histone and anti-chromatin antibodies were measured by ELISA. Frequencies of B cells, activated and regulatory CD4+ T cells as well as Th1, Th2, Th17 cells were measured by flow cytometry. RT-qPCR was used to measure expression levels of interferon-signature and T-cell subset related as well as miR155-associated genes.

RESULTS:

After induction of lupus, miR155-deficient mice had significant less pulmonary involvement (perivascular inflammatory area in mm2/mm2 lung area 0.00092±0.00015 vs. 0.0027±0.00075, p = 0.0347) and renal disease (glomerular activity score 1.95±0.19 vs 3±0.26, p = 0.0029) compared to wild types. MiR155-deficient mice had significantly lower serum levels of disease-associated auto-antibodies and decreased frequencies of activated CD4+CD25+ (Foxp3-) cells. Upon restimulation, CD4+ cells showed a less pronounced Th2 and Th17 and a slightly decreased Th1 response in mir155-deficient mice. Pristane-treated wild types showed significantly up-regulated expression of genes related to the INF-signature (MX1, IP10, IRF7, ISG15).

CONCLUSIONS:

MiR155-deficient mice had less severe organ involvement, lower serum auto-antibody levels, a less prominent T cell response and lower expressions of genes jointly responsible for disease development. Thus, antagonizing miR155 might be a future approach in treating SLE.

• Authors: Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
• Journal: PloS one (PLoS One) Vol. 12 Issue 7 Pg. e0181015 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28719617 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• MicroRNAs
• Mirn155 microRNA, mouse
• Terpenes
• pristane
• Interferons

Topics

• Animals
• Autoantibodies (metabolism)
• Gene Expression Regulation (drug effects, immunology)
• Interferons (metabolism)
• Kidney (drug effects, immunology)
• Lung (drug effects, immunology)
• Lupus Erythematosus, Systemic (chemically induced, complications)
• Mice
• MicroRNAs (metabolism)
• Nephritis (complications, drug therapy, immunology, metabolism)
• Pneumonia (complications, drug therapy, immunology, metabolism)
• T-Lymphocyte Subsets (drug effects, immunology)
• Terpenes (pharmacology)