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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/4084

Title: Immune mediated protection in multiple sclerosis: A role for neurokines in oligodendrocyte survival and macrophage modulation
Authors: HELLINGS, Niels
HENDRIKS, Jerome
CARMANS, Sofie
SLAETS, Leen
DUMONT, Debora
VANDERLOCHT, Joris
STINISSEN, Piet
Issue Date: 2007
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation: CLINICAL IMMUNOLOGY, 123(S1). p. S137-S137
Abstract: In multiple sclerosis (MS), immune mediated destruction of the myelin sheath, oligodendrocytes and axons leads to irreversible neurological deficits. Recent data show that immune responses in the central nervous system (CNS) may also confer protective effects. We recently demonstrated that autoreactive T cells and macrophages produce leukemia inhibitory factor (LIF), a member of the IL-6 family of neurokines. CD4+ T cells from relapsing remitting MS-patients show a reduced LIF production. Still, LIF immunoreactivity is detected among T cells and perivascular macrophages in MS lesions. In rat oligodendrocyte cultures, LIF protects against TNF-α and IFN-γ induced apoptosis, but not against other cell death mediators (oxidative stress, staurosporin). LIF receptor signalling in oligodendrocytes does not induce the expression of suppressors of cytokine signalling (SOCS) or the anti-apoptotic molecules Bcl-2/Bcl-XL. Using quantitative proteomics, we demonstrate that LIF leads to upregulation of a panel of proteins that have pro-survival functions. Future experiments are needed to study their role in LIF mediated oligodendrocyte protection. Since macrophages, but not T cells, express functional LIF-receptor complexes we studied whether LIF also exerts immunomodulatory functions. LIF significantly upregulates myelin phagocytosis and reduces the production of reactive oxygen species and TNF-α in vitro. In summary, neurokines may act on various levels during CNS inflammation: they may modulate immune responses and protect CNS resident cells under attack. Further clarification in the actions of different neurokine members during neuroinflammation may lead to new therapeutic strategies for MS.
Notes: Hasselt Univ, Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/4084
DOI: 10.1016/j.clim.2007.03.027
ISI #: 000247137200355
ISSN: 1521-6616
Category: M
Type: Journal Contribution
Appears in Collections: Research publications

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