Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.639369
Keywords
multiple sclerosis; Alzheimer' s disease; neuroinflammation; neutrophils; monocytes; T cells
Categories
Funding
- European Research Council (ERC) [695714]
- ERC [693606]
- Alzheimer's Drug Discovery Foundation (ADDF), USA
- Fondazione Italiana Sclerosi Multipla (FISM), Genoa, Italy [2013/R/21, 2019/PR-single/044]
- University of Verona, Italy (FUR)
- INVITE European Union [754345]
- Fondazione Umberto Veronesi
- European Research Council (ERC) [693606] Funding Source: European Research Council (ERC)
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Neurodegenerative diseases are closely linked to inflammatory and autoimmune processes, with immune system dysregulation playing a key role in their pathology. Both multiple sclerosis and Alzheimer's disease share common features such as infiltrating immune cells and activated neutrophils. Regulatory T cells are beneficial in the early stages of MS and AD, helping to control neuroinflammation and potentially influencing disease progression.
Neurodegenerative diseases are closely related to inflammatory and autoimmune events, suggesting that the dysregulation of the immune system is a key pathological factor. Both multiple sclerosis (MS) and Alzheimer's disease (AD) are characterized by infiltrating immune cells, activated microglia, astrocyte proliferation, and neuronal damage. Moreover, MS and AD share a common pro-inflammatory signature, characterized by peripheral leukocyte activation and transmigration to the central nervous system (CNS). MS and AD are both characterized by the accumulation of activated neutrophils in the blood, leading to progressive impairment of the blood-brain barrier. Having migrated to the CNS during the early phases of MS and AD, neutrophils promote local inflammation that contributes to pathogenesis and clinical progression. The role of circulating T cells in MS is well-established, whereas the contribution of adaptive immunity to AD pathogenesis and progression is a more recent discovery. Even so, blocking the transmigration of T cells to the CNS can benefit both MS and AD patients, suggesting that common adaptive immunity mechanisms play a detrimental role in each disease. There is also growing evidence that regulatory T cells are beneficial during the initial stages of MS and AD, supporting the link between the modulatory immune compartments and these neurodegenerative disorders. The number of resting regulatory T cells declines in both diseases, indicating a common pathogenic mechanism involving the dysregulation of these cells, although their precise role in the control of neuroinflammation remains unclear. The modulation of leukocyte functions can benefit MS patients, so more insight into the role of peripheral immune cells may reveal new targets for pharmacological intervention in other neuroinflammatory and neurodegenerative diseases, including AD.
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