Nanomodulation of Macrophages in Multiple Sclerosis

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.

Differences in the sensitivity of classically and alternatively activated macrophages to TAK1 inhibitor-induced necroptosis

“…Targeted modulation of M1/M2 transition may offer promising strategies to cure various life-threatening diseases. Accordingly, ongoing clinical trials aim to modulate M1/M2 balance in cancer [5,6], atherosclerosis [2], sclerosis multiplex [39] or endometriosis [40]. Currently, the therapeutic approaches to alter the ratio of macrophage subsets are bipartite, on the one hand directing the differentiation of these cells, and on the other hand, altering the function of the differentiated cells [6].…”

Promising Nanotechnology Approaches in Treatment of Autoimmune Diseases of Central Nervous System

“…It seems that T helper 1 (TH1) and TH17 cells are the main pathogenic populations in the immunopathogenesis of MS, along with regulatory T cells (Treg) and natural killer T (NKT) cells [34][35][36][37]. The pro-inflammatory state of macrophages is correlated with MS because macrophages interact with T and B cells, instructing demyelination, axonal loss, and degeneration, and they are presented as of the most predominant cell type in patient lesions [38,39]. In Figure 1, there is a detailed presentation of the cells that are involved in the immune process of MS [25].…”

“…In addition, a number of humanized monoclonal antibody-based therapeutics for RRMS were developed, including natalizumab, alemtuzumab, and ocrelizumab. Unfortunately, their disadvantage is the high risk of side effects, including progressive multifocal leukoencephalopathy (PML) and the development of secondary autoimmune diseases [4,12,25,26,39,[41][42][43][44][45].…”

Progressive Multiple Sclerosis Transcriptome Deconvolution Indicates Increased M2 Macrophages in Inactive Lesions

“…Multiple sclerosis (MS) is a heterogeneous autoimmune disease characterized by demyelination and neurodegeneration [1]. As the disease advances, pathological changes are observed in the brain white matter (WM) that can be categorized into distinct lesion types based on measures of myelin loss and immune infiltrate [2].…”