Abstract
Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain’s parenchyma, known as microglia and monocyte-derived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.
Highlights
Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS)
During the effector stage of EAE, monocytes rapidly infiltrate surrounding meninges, perivascular space, and choroid plexus through and differentiate into MФs [142, 143]. These MФs contribute to the progression of the paralytic stage of EAE and demyelination by expressing major histocompatibility complex (MHC)-II, costimulatory molecules, and producing pro-inflammatory factors [38]
The role of MФs and microglia in neuroinflammation and MS pathogenesis calls our attention to the use of different therapeutic agents that target these cells
Summary
Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). In vitro exposure of monocytes and MФs to Th1 cytokines, lipopolysaccharide (LPS), and granulocyte-macrophage colonystimulating factor (GM-CSF) induces their polarization to inflammatory M1 phenotype. These cells produce high levels of pro-inflammatory cytokines, including TNF-a, IL-6, IL-1b, and inducible nitric oxide synthase (iNOS) [22, 23]. Based on studies, glycolysis may promote the immune function of M1 MФs by increasing the secretion of inflammatory cytokines and enhancing phagocytic activity [33]. According to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target Due to their dissimilar origin, location, and turnover, different strategies may require to target the various myeloid cell populations. We review the role of distinct subsets of MФs in the pathogenesis of MS and the impact of different therapeutic agents on these cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
