GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is asso...
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doaj-bf00bc9928cb4bf98d6a88c7579b561e2020-11-25T02:29:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018264610.1371/journal.pone.0182646GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency.Tatjana ScholzAndreas WeigertBernhard BrüneChristian D SadikBeate BöhmHarald BurkhardtGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is associated with favorable therapeutic effects in patients with rheumatoid arthritis. We evaluated the role of GM-CSF as a potential target for therapeutic interference in psoriasis using a combined pharmacologic and genetic approach and the mouse model of imiquimod-induced psoriasiform dermatitis (IMQPD). Neutralization of murine GM-CSF by an anti-GM-CSF antibody ameliorated IMQPD. In contrast, genetic deficiency in GM-CSF did not alter the course of IMQPD, suggesting the existence of mechanisms compensating for chronic, but not acute, absence of GM-CSF. Further investigation uncovered an alternative pathogenic pathway for IMQPD in the absence of GM-CSF characterized by an expanded plasmacytoid dendritic cell population and release of IFNα and IL-22. This pathway was not activated in wild-type mice during short-term anti-GM-CSF treatment. Our investigations support the potential value of GM-CSF as a therapeutic target in psoriatic disease. The discovery of an alternative pathogenic pathway for psoriasiform dermatitis in the permanent absence of GM-CSF, however, suggests the need for monitoring during therapeutic use of long-term GM-CSF blockade.http://europepmc.org/articles/PMC5544216?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tatjana Scholz Andreas Weigert Bernhard Brüne Christian D Sadik Beate Böhm Harald Burkhardt |
spellingShingle |
Tatjana Scholz Andreas Weigert Bernhard Brüne Christian D Sadik Beate Böhm Harald Burkhardt GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. PLoS ONE |
author_facet |
Tatjana Scholz Andreas Weigert Bernhard Brüne Christian D Sadik Beate Böhm Harald Burkhardt |
author_sort |
Tatjana Scholz |
title |
GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
title_short |
GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
title_full |
GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
title_fullStr |
GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
title_full_unstemmed |
GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
title_sort |
gm-csf in murine psoriasiform dermatitis: redundant and pathogenic roles uncovered by antibody-induced neutralization and genetic deficiency. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is associated with favorable therapeutic effects in patients with rheumatoid arthritis. We evaluated the role of GM-CSF as a potential target for therapeutic interference in psoriasis using a combined pharmacologic and genetic approach and the mouse model of imiquimod-induced psoriasiform dermatitis (IMQPD). Neutralization of murine GM-CSF by an anti-GM-CSF antibody ameliorated IMQPD. In contrast, genetic deficiency in GM-CSF did not alter the course of IMQPD, suggesting the existence of mechanisms compensating for chronic, but not acute, absence of GM-CSF. Further investigation uncovered an alternative pathogenic pathway for IMQPD in the absence of GM-CSF characterized by an expanded plasmacytoid dendritic cell population and release of IFNα and IL-22. This pathway was not activated in wild-type mice during short-term anti-GM-CSF treatment. Our investigations support the potential value of GM-CSF as a therapeutic target in psoriatic disease. The discovery of an alternative pathogenic pathway for psoriasiform dermatitis in the permanent absence of GM-CSF, however, suggests the need for monitoring during therapeutic use of long-term GM-CSF blockade. |
url |
http://europepmc.org/articles/PMC5544216?pdf=render |
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