Our current research aims at elucidating how cellular lipid metabolism impacts inflammatory and repair processes within the central nervous system (CNS) with a focus on Multiple Sclerosis (MS).
During MS, macrophages infiltrate the brain and together with microglia, the resident immune cells of the CNS, degrade myelin, an insulating layer surrounding nerves that is important for the propagation of action potentials. Myelin breakdown, also called demyelination, leads to failure of nerve conduction and to a wide range of clinical symptoms such as loss of vision and muscle weakness. Besides contributing to demyelination, macrophages and microglia can also promote repair of damaged tissue (remyelination) by clearing myelin debris and secreting anti-inflammatory and neurotrophic factors.
Myelin consists for the major part of lipids, such as cholesterol and fatty acids. In MS, a disturbed lipid metabolism is detected. However, little is known about the cause of this disturbance and the impact it has on disease progression. Our findings show that lipids present in myelin alter the function of macrophages and microglia. By targeting the underlying pathways a beneficial macrophage phenotype can be induced that slows down lesion progression and stimulates repair. Interestingly, specific nutritional components impact lipid metabolism and immune cell function and thus provide a promising strategy to limit lesion progression and promote CNS repair. Current research focusses on further elucidating metabolic pathways that direct immune cell function and to translate current findings into therapeutic applications.
We aim to:
1) determine the role of cholesterol and fatty acids in CNS inflammation, demyelination and remyelination.
2) study how dietary components affect CNS lipid metabolism and the function of resident brain cells.
Experimental autoimmune encephalomyelitis (EAE): mouse model of CNS inflammation
Cuprizone model: mouse model of de- and remyelination
Organotypic brain slice cultures- ex vivo model of remyelination
Primary cell cultures of oligodendrocytes, microglia and astrocytes
Macrophage inflammatory and metabolic phenotyping
Jeroen F.J. Bogie , Elien Grajchen , Elien Wouters , Aida Garcia Corrales , Tess Dierckx , Sam Vanherle , Jo Mailleux , Pascal Gervois, , Esther Wolfs , Jonas Dehairs , Jana Van Broeckhoven, , Andrew P. Bowman, Ivo Lambrichts , Jan-Åke Gustafsson , Alan T. Remaley, Monique Mulder, Johannes V. Swinnen , Mansour Haidar, Shane R. Ellis , James M. Ntambi , Noam Zelcer, Jerome J.A. Hendriks. Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain. J Exp Med (2020) 217 (5): e20191660. (IF 10.9)
Bogie JFJ, Haidar M, Kooij G*, Hendriks JJA*. Fatty acid metabolism in the progression and resolution of CNS disorders. Adv Drug Deliv Rev. 2020 Jan 25. pii: S0169-409X(20)30006-5. doi: 10.1016/j.addr.2020.01.004. (IF15.6) *equal contribution
Wouters E*, de Wit NM*, Vanmol J, van der Pol SMA, van Het Hof B, Sommer D, Loix M, Geerts D, Gustafsson JA, Steffensen KR, Vanmierlo T, Bogie JFJ, Hendriks JJA*, de Vries HE*. Liver X Receptor Alpha Is Important in Maintaining Blood-Brain Barrier Function. Front Immunol. 2019 Jul 31;10:1811. doi: 10.3389/fimmu.2019.01811. (IF 4.7) *equal contribution.
Grajchen E, Hendriks JJA, Bogie JFJ. The physiology of foamy phagocytes in multiple sclerosis. Acta Neuropathol Commun. 2018 Nov 19;6(1):124 doi: 10.1186/s40478-018-0628-8. Review. (IF 5.36)
Jo Mailleux, Silke Timmermans, Katherine Nelissen, Jasmine Vanmol, Tim Vanmierlo, Jack van Horssen, Jeroen FJ Bogie and Jerome JA Hendriks. Low-density lipoprotein receptor deficiency attenuates neuroinflammation through the induction of apolipoprotein Front Immunol. 2017 Nov 30;8:1701. doi: 10.3389/fimmu.2017.01701. (IF 4.7)
Mailleux J, Vanmierlo T, Bogie JF, Wouters E, Lütjohann D, Hendriks JJA*, van Horssen J*. Active liver X receptor signaling in phagocytes in multiple sclerosis lesions. Mult Scler. 2017 Feb 1 (IF 4.8) *equal contribution
Jorissen W, Wouters E, Bogie JF, Vanmierlo T, Noben JP, Sviridov D, Hellings N, Somers V, Valcke R, Vanwijmeersch B, Stinissen P, Mulder MT, Remaley AT, Hendriks JJA. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Sci Rep. 2017 Feb 23;7:43410. (IF 4.2)
Vanmierlo T, Bogie J, Mailleux J, Vanmol J, Lütjohann D, Mulder MT, Hendriks JJA. Plant sterols: friend or foe in CNS disorders? Progress in Lipid Research 2015 (IF 13.0)
Bogie JF, Stinissen P, Hendriks JJA. Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathol. 2014 Aug;128(2):191-213. (IF 10.7)
Timmermans S, Bogie JF, Vanmierlo T, Lütjohann D, Stinissen P, Hellings N, Hendriks JJA. High Fat Diet Exacerbates Neuroinflammation in an Animal Model of Multiple Sclerosis by Activation of the Renin Angiotensin System. J Neuroimmune Pharmacol. 2013 Sep 26. (IF 3.8)
Myelin alters the inflammatory phenotype of macrophages by activating PPARs. Bogie JFJ, Jorissen W, Mailleux J, Nijland PG, Zelcer N, Vanmierlo T, Van Horssen J, Stinissen P, Hellings N, Hendriks JJA. Acta Neuropathol Commun. 2013 Aug 2;1(1):43. (IF 5.36)
Bogie JF, Timmermans S, Huynh-Thu V, Irrthum A, Smeets HJM, Gustafsson JA, Steffensen KR, Mulder MT, Stinissen P, Hellings N, Hendriks JJA. Myelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation. PLoS One. 2012;7(9):e44998. (IF 3.8)
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Current vacancies will be posted here, and at https://www.uhasselt.be/vacancies.
Also, we provide support in applying for PhD or postdoctoral fellowships. Contact us to discuss the possibilities.