The Role of the Immune System in Huntington’s Disease

Figure 1

Neuroinflammation in the center of HD pathophysiology. Immune activation, induced by mutant huntingtin (mhtt), is found ubiquitously: in the central nervous system (central), the blood circulation (peripheral), and at molecular level (cellular). In the CNS, mhtt may not only influence migration of cells, for example, myeloid cells, but also induces microglia activation. Cytokines and chemokines (e.g., IL-6, TNFα) are secreted, and reactive oxygen species (ROS) are activated. Furthermore, glutamate-induced excitotoxicity, that is, in close interaction with oxidative stress, may contribute to degeneration. Migration deficits are discussed to influence innate immune response in the periphery very early in HD. Once again, cytokines, chemokines, and ROS in concert may trigger neuroinflammation. On a cellular level, mhtt upregulates the NF-kappa B (NF-κB) signaling pathway that triggers IL-6 expression. Finally, mitochondrial dysfunction generated by mhtt seems to be a key player leading to neuroinflammation in HD. The complement system is a connection between the innate and adaptive immune response. There are two ways that activate the complement system: first, inflammation with all its resulting effects targets factors of the complement system. Second, antibody response and T-cell response follow in secretion of complement factors. Various cell types may be affected, among these monocytes, astrocytes, and T and B cells.