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Review
. 2010 Apr 15;221(1-2):7-14.
doi: 10.1016/j.jneuroim.2009.10.015.

Role of the Innate Immune System in the Pathogenesis of Multiple Sclerosis

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Free PMC article
Review

Role of the Innate Immune System in the Pathogenesis of Multiple Sclerosis

Roopali Gandhi et al. J Neuroimmunol. .
Free PMC article

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease with heterogeneous clinical presentations and course. MS is considered to be a T cell mediated disease but in recent years contribution of innate immune cells in mediating MS pathogenesis is being appreciated. In this review, we have discussed the role of various innate immune cells in mediating MS. In particular, we have provided an overview of potential anti-inflammatory or pro-inflammatory function of DCs, microglial Cells, NK cells, NK-T cells and gamma delta T cells along with their interaction among themselves and with myelin. Given the understanding of the role of the innate immune cells in MS, it is possible that immunotherapeutic intervention targeting these cells may provide a better and effective treatment.

Figures

Figure 1
Figure 1
Potential contribution of cytokines secreted by innate immune cells in MS and their role in T cell differentiation: effector or regulatory T cells. Inflammatory cytokines (in red) secreted by innate immune cells lead to differentiation of effector T cell populations such as Th1, Th2 and Th17 involved either in mediating inflammation or in immunomodulation. Whereas anti-inflammatory cytokines (in green) secreted by innate immune cells play an important role in induction of regulatory T cells that are capable of mediating tolerogenic function during disease.
Figure 2
Figure 2
A hypothetical model of potential neuro-protective and neuro-destructive function of innate immune cells against myelin components. Innate immune cells mediate direct cytotoxicity against myelin or oligodendrocytes by either enzymes like perforins or reactive oxygen species or direct contact-mediated by Fas-FasL interactions resulting in myelin disruption. Phagocytosis of degraded myelin results in increased activation and secretion of more cytotoxic components by these cells. Innate immune cells also play a neuro-protective role by secretion of various neurotropic factors that help in promoting neurogenesis.

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