Role of Peripheral Immune Cells-Mediated Inflammation on the Process of Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are characterized by progressive loss of selectively vulnerable neuronal populations, which contrasts with selectively static loss of neurons due to toxic or metabolic disorders. The mechanisms underlying their progressive nature remain unknown. To date, a timely and well-controlled peripheral inflammatory reaction is verified to be essential for neurodegenerative diseases remission. The influence of peripheral inflammation on the central nervous system is closely related to immune cells activation in peripheral blood. The immune cells activation participated in the uncontrolled and prolonged inflammation that drives the chronic progression of neurodegenerative diseases. Thus, the dynamic modulation of this peripheral inflammatory reaction by interrupting the vicious cycle might become a disease-modifying therapeutic strategy for neurodegenerative diseases. This review focused on the role of peripheral immune cells on the pathological progression of neurodegenerative diseases.

Keywords: B cell; T cell; dendritic cell; macrophage; monocyte; natural killer cell; neurodegenerative diseases; peripheral immune cells.

Figure 1

Roles of peripheral immune cells on the pathogenesis of neurodegenerative diseases. The antigen stimulated the immune response of macrophages and B cells. Macrophages engulfed antigens and presented them to T cells. The cytokines of IL-4, IL-6, IL-12, and TGF-β released by T cells regulated the development of Th2, Treg, Th1, and Th17 cells, respectively. Then, these cells secreted anti-inflammatory or pro-inflammatory factors to regulate neuronal survival. In addition, antigens could directly stimulate B cells. Upon activation, B cells produced pro-inflammatory factors, which entered the brain along blood vessels and participated in neurodegeneration. On the other hand, activated T cells secreted lymphokines to activate B cells and activated B cells could proliferate and differentiate into plasma cells. Subsequently, the plasma cells-produced cytokines and antibodies, such as anti-Aβ or anti-α-synuclein antibodies, went across blood brain barrier and entered the brain and thus attenuated neurons degeneration.