MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus.
We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus.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 a...
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doaj-2fa5041e40ed423a97727ced20f26c682020-11-25T01:45:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018101510.1371/journal.pone.0181015MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus.Harald LeissWilhelm SalzbergerBarbara JacobsIrina GesslNicolas KozakowskiStephan BlümlAntonia PuchnerAttila KissBruno K PodesserJosef S SmolenGeorg H StummvollWe herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus.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.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).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.http://europepmc.org/articles/PMC5515414?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. PLoS ONE |
author_facet |
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 |
author_sort |
Harald Leiss |
title |
MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
title_short |
MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
title_full |
MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
title_fullStr |
MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
title_full_unstemmed |
MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
title_sort |
microrna 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus.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.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).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. |
url |
http://europepmc.org/articles/PMC5515414?pdf=render |
work_keys_str_mv |
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