Abstracts (complete list) - Wissenschaft Online

Katrin Drögemüller, Martina Deckert, Ulrike Hellmuth, Monika Sakowicz-Burkiewicz,
Dirk Reinhold, David Gutmann, Werner Müller, Dirk Schlüter
Astrocyte gp130-expression is critical for astrocyte survival,
downregulation of intracerebral immune responses and
survival of experimental autoimmune encephalomyelitis and
Toxoplasma encephalitis
In cerebral inflammatory diseases, there is robust astrocyte activation; however their in
vivo function is largely unknown. To study their role in experimental autoimmune
encephalomyelitis (EAE), we generated mice deficient in astrocytic expression of gp130
(GFAP-Cre gp130fl/fl), the signal transducing receptor for cytokines of the IL-6 family.
numbers of GFAP+ astrocytes were strongly reduced in experimental autoimmune
encephalomyelitis (EAE) of GFAP-Cre gp130fl/fl mice. Clinically, GFAP-Cre gp130fl/fl
mice were characterized by a significantly more severe EAE and finally succumbed to
chronic EAE, whereas control mice recovered. Histopathologically, inflammation and
demyelination were more intense, widespread and persisted in GFAP-Cre gp130fl/fl
mice. In addition, GFAP-Cre gp130fl/fl mice were significantly impaired in control of
Toxoplasma gondii ultimately dying of a necrotizing Toxoplasma encephalitis (EAE).
While GFAP+ astrocytes of infected gp130fl/fl control mice were activated and increased
in number, which was associated with effective parasite control and survival of TE,
GFAP-Cre gp130fl/fl mice lossed GFAP+ astrocytes during TE. In vitro, survival of T.
gondii-infected, LPS- and TNF-stimulated astrocytes was also gp130-dependent. Thus,
astrocytes are of crucial importance in EAE and TE, and gp130 is a critical survival
factor of astrocytes in inflammatory CNS disorders.