Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Jeroen F. J. Bogie,Winde Jorissen,Jo Mailleux,Philip G. Nijland,Noam Zelcer,Tim Vanmierlo,Jack van Horssen,Piet Stinissen,Niels Hellings,Jerome J. A. Hendriks +9 more
TLDR
The data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression and the immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics.Abstract:
Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPARβ/δ is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPARβ/δ in macrophages in the human brain. Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPARβ/δ activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics.read more
Citations
More filters
Journal ArticleDOI
TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord.
Antje Kroner,Andrew D. Greenhalgh,Juan G. Zarruk,Rosmarini Passos dos Santos,Matthias Gaestel,Samuel David +5 more
TL;DR: It is shown that TNF prevents phagocytosis-mediated conversion from M1 to M2 cells in vitro and in vivo in spinal cord injury (SCI), and transplantation experiments show that increased loading of M2 macrophages with iron induces a rapid switch from M2 to M1 phenotype.
Journal ArticleDOI
Macrophage subsets and microglia in multiple sclerosis.
TL;DR: It is concluded that microglia and macrophages are highly dynamic cells displaying disease stage and location-specific fates in neurological disorders, and changing the physiology of divergent phagocyte subsets at particular disease stages holds promise for future therapeutics for CNS pathologies.
Journal ArticleDOI
Myelination, Oligodendrocytes, and Serious Mental Illness
Vahram Haroutunian,Vahram Haroutunian,Pavel Katsel,Panos Roussos,Panos Roussos,Kenneth L. Davis,L. L. Altshuler,L. L. Altshuler,L. L. Altshuler,G. Bartzokis,G. Bartzokis,G. Bartzokis +11 more
TL;DR: The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems‐level understanding of the interdependent age‐related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases.
Journal ArticleDOI
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.
Muktha S Natrajan,Muktha S Natrajan,Alerie Guzman de la Fuente,Abbe H. Crawford,Eimear Linehan,Vanessa Núñez,Kory R. Johnson,Tianxia Wu,Denise C. Fitzgerald,Mercedes Ricote,Bibiana Bielekova,Robin J.M. Franklin +11 more
TL;DR: The retinoid X receptor pathway is revealed as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
Journal ArticleDOI
The origin, fate, and contribution of macrophages to spinal cord injury pathology
TL;DR: This review considers the possibility that different macrophage origins, including the spleen, bone marrow, and local self-renewal, may also affect macrophages fate, and ultimately their function that contribute to the complex pathobiology of spinal cord injury.
References
More filters
Journal ArticleDOI
Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes
Jo Vandesompele,Katleen De Preter,Filip Pattyn,Bruce Poppe,Nadine Van Roy,Anne De Paepe,Franki Speleman +6 more
TL;DR: The normalization strategy presented here is a prerequisite for accurate RT-PCR expression profiling, which opens up the possibility of studying the biological relevance of small expression differences.
Journal ArticleDOI
Exploring the full spectrum of macrophage activation.
TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
Journal ArticleDOI
Monocyte and macrophage heterogeneity
Siamon Gordon,Philip R. Taylor +1 more
TL;DR: Recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues.
Journal ArticleDOI
Axonal transection in the lesions of multiple sclerosis.
TL;DR: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Journal ArticleDOI
Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
TL;DR: The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.
Related Papers (5)
Differential roles of microglia and monocytes in the inflamed central nervous system.
Ryo Yamasaki,Haiyan Lu,Oleg Butovsky,Nobuhiko Ohno,Anna Rietsch,Ron Cialic,Pauline M. Wu,Camille Doykan,Jessica Lin,Anne C. Cotleur,Grahame J. Kidd,Musab M. Zorlu,Nathan Sun,Weiwei Hu,LiPing Liu,Jar Chi Lee,Sarah E. Taylor,Lindsey Uehlein,Lindsey Uehlein,Debra Dixon,Jinyu Gu,Crina M. Floruta,Min Zhu,Israel F. Charo,Howard L. Weiner,Richard M. Ransohoff +25 more