Abstract
Multiple Sclerosis (MS) is a chronic demyelinating autoimmune disease primarily affecting young adults. Despite an unclear causal factor, symptoms and pathology arise from the infiltration of peripheral immune cells across the blood brain barrier. Accounting for the largest fraction of this infiltrate, macrophages are functionally heterogeneous innate immune cells capable of adopting either a pro or an anti-inflammatory phenotype, a phenomenon dependent upon cytokine milieu in the CNS. This functional plasticity is of key relevance in MS, where the pro-inflammatory state dominates the early stage, instructing demyelination and axonal loss while the later anti-inflammatory state holds a key role in promoting tissue repair and regeneration in later remission. This review highlights a potential therapeutic benefit of modulating macrophage polarisation to harness the anti-inflammatory and reparative state in MS. Here, we outline the role of macrophages in MS and look at the role of current FDA approved therapeutics in macrophage polarisation. Moreover, we explore the potential of particulate carriers as a novel strategy to manipulate polarisation states in macrophages, whilst examining how optimising macrophage uptake via nanoparticle size and functionalisation could offer a novel therapeutic approach for MS.
Highlights
Multiple Sclerosis (MS) is a chronic inflammatory disease of the Central Nervous System (CNS), affecting an estimated 2.3 million people worldwide [1]
In conjunction with the increased serum IL-10 levels seen in IFNβ treated MS patients [145,146], this indicates IL-10 modulation of macrophages and their monocyte precursors may occur in response to IFNβ treatment
Similar effects on monocyte populations have been demonstrated in Dimethyl fumarate (DMF) treated MS patients, with peripheral monocytes showing reduced levels of mir-155, a micro-RNA associated with major pro-inflammatory effect [125], while in vitro treated human monocytes showed suppressed TNFα, IL-6 and IL-10 responses to a pro-inflammatory stimulus [125]
Summary
Multiple Sclerosis (MS) is a chronic inflammatory disease of the Central Nervous System (CNS), affecting an estimated 2.3 million people worldwide [1]. Emerging and accumulating evidence has highlighted a role for infiltrating monocytes and macrophages in human MS pathology, as comprehensively discussed in [16] and as further discussed in this review These cells are the most predominant cell type in patient lesions [17,18,19,20], with their presence correlating with both demyelination [21,22] and axonal damage and degeneration [20,22,23,24]. This, coupled with the fact that demyelination and lesion formation occur predominantly in the spinal cord rather than the CNS, indicates that EAE does not fully recapitulate human MS pathology [25,29,31]. We examine this role played by macrophages in MS and MS animal models, and explore the potential for the use of nanotechnology in developing macrophage-centred therapeutics for preclinical efficacy in MS
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