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Regulation of SOCS3 expression by glucocorticoids – a novel mechanism to induce dendritic tolerance?
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Glucocorticoids (GC) are widely prescribed anti-inflammatory drugs. However, their exact mechanism of action is not yet sufficiently understood. We showed recently that one reason for the GC-function is an increased IL-6-induced JAK/STAT-signalling in the liver. The increase in STAT3 activation is caused by a reduced expression of the IL-6-induced feedback-inhibitor SOCS3. SOCS3 is known to be a major mediator of inflammation. Though, the exact function of SOCS3 is still under investigation. In many cell types a prolonged activation of STAT3, caused e.g. by a reduced SOCS3 expression, leads to severe diseases and overexpression of SOCS3 reduces progression of arthritis in mice.GC also affect antigen-presenting cells such as dendritic cells, where they promote the differentiation of a tolerogenic phenotype. These tolerogenic dendritic cells have a low costimulatory potential, secrete high levels of anti-inflammatory cytokines and exhibit an impaired potential to induce the differentiation of inflammatory T cells. However, the molecular mechanism of GC- modified dendritic cell maturation is still under investigation. Interestingly, the group of Prof. Yoshimura showed that SOCS3-deficient dendritic cells also develop into tolerogenic DC. Furthermore, other groups showed that the timely orchestrated expression of SOCS3 is important for the development of mature immunogenic dendritic cells and that SOCS3 is one of the master regulators defining the inflammatory phenotype of dendritic cells. Based on these studies we postulate that GC influence the development of tolerogenic DC by reducing the expression of SOCS3 in DC. This is an up to know unknown molecular mechanism that may contribute to the anti-inflammatory properties of GC.

Schlagworte

Glucocorticoide, Interleukin-6, LPS, SOCS3, dendritische Zellen

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Kontakt
Dr. Anna Dittrich

Dr. Anna Dittrich

Otto-von-Guericke-Universität Magdeburg

Fakultät für Naturwissenschaften

Institut für Biologie

Universitätsplatz 2

39106

Magdeburg

Tel.+49 391 6750215

Fax:+49 391 6743004

anna.dittrich(at)ovgu.de

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