期刊
PLOS ONE
卷 12, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0182646
关键词
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资金
- Landes-Offensive zur Entwickl ung Wissenschattlich-okonom ischer Exzellenz (LOEWE) of the Federal State of Hesse
- Research Center for Translational Medicine and Pharmacology TMP
- Else Kroner-Fresenius Foundation (EKFS)
- Research Training Group Translational Research Innovation-Pharma (TRIP)
- Federal Ministry of Education and Research of Germany (Arthromark TP4) [01 EC1401C]
- Deutsche Forschungsgemeinschaft [Sal 960/5-1]
- Galderma Fbrderkreis e.V.
- Fraunhofer Institute I ME, Frankfurt am Main, Germany
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 IFN alpha 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.
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