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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/14345

Title: Interleukin-6 class cytokines regulate the development of inflammatory CNS lesions
Authors: Hellings, N.
Janssens, K.
Hendriks, J. J. A.
de Vries, H.
Vanwijmeersch, B.
Eijnde, B. O.
Van den Haute, C.
Baekelandt, V.
Stinissen, P.
Slaets, H.
Issue Date: 2012
Publisher: WILEY-BLACKWELL
Citation: IMMUNOLOGY, 137 (s1), p. 31-31
Abstract: Purpose/Objective: The interleukin-6 class cytokines leukemia inhibitory factor (LIF) and oncostatin M (OSM) are upregulated in multiple sclerosis (MS) lesions, but their effects on CNS lesion development are far from understood. LIF and OSM potentially influence immune responses as well as CNS resident cells during neuroinflammatory conditions. Importantly, since they activate different receptors, LIF and OSM can influence these parameters to different extents. This study was designed to elucidate the role of OSM and LIF in MS lesion development. Materials and methods: Stereotactic application of lentiviral vectors was performed to achieve a stable expression and secretion of LIF or OSM in the CNS of adult mice. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL6J mice with MOG-peptide. Receptor expression on human immune cell subsets was determined by flow cytometry. Primary cultures of oligodendrocytes and macrophages were used to study direct effects on these cell types. Immunohistochemistry and real time PCR were applied to elucidate the in vivo effects of local cytokine expression. Results: Our previous study showed that gene therapeutic expression of LIF in the CNS significantly reduced immune-mediated demyelination. Our in vitro studies show that LIF protects oligodendrocytes from inflammatory insults. Now, we demonstrated that treatment after disease onset still ameliorates EAE symptoms. To define which immune cells play a crucial role in the immunomodulatory actions of LIF, expression of the LIF receptor was determined on human immune cells. Monocytes express the LIF receptor subunits at high levels, while there is only a limited population of T cells and B cells that express the receptor. LIF reduces production of toxic mediators by macrophages. In contrast to LIF, local expression of OSM did not simply alleviate symptoms but suppressed the incidence of EAE. While we did find a local inflammatory response at the site ofOSMexpression, infiltration of typical EAE-related immune cells in the CNS was blocked. CNS-targeted OSM production was necessary, since systemic administration of the cytokine did not affect development of autoimmune induced CNS lesions. Conclusions: Our study demonstrates that OSM and LIF play an important but distinct role in lesion development in neuroinflammatory disease. These cytokines and their downstream signalling molecules are potential candidates for therapy.
Notes: [Hellings, N.; Janssens, K.; Hendriks, J. J. A.; Vanwijmeersch, B.; Eijnde, B. O.; Stinissen, P.; Slaets, H.] Hasselt Univ, Biomed Res Inst BIOMED, Diepenbeek, Belgium. [de Vries, H.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Van den Haute, C.; Baekelandt, V.] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium.
URI: http://hdl.handle.net/1942/14345
DOI: 10.1111/imm.12001
ISI #: 000309189100074
ISSN: 0065-2776
Category: M
Type: Journal Contribution
Appears in Collections: Biomedical Research Institute
Healthcare & Economics
Immunology - Biochemistry

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