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 inMS 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 bothMS 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.

Common peripheral immunity mechanisms in multiple sclerosis and Alzheimer’s disease

Barbara Rossi
Writing – Review & Editing
;
Bruno Santos-Lima
Writing – Original Draft Preparation
;
Eleonora Terrabuio
Writing – Original Draft Preparation
;
Elena Zenaro
Writing – Original Draft Preparation
;
Gabriela Constantin
Writing – Review & Editing
2021-01-01

Abstract

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 inMS 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 bothMS 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.
multiple sclerosis, Alzheimer’s disease, neuroinflammation, neutrophils, monocytes, T cells
File in questo prodotto:
File Dimensione Formato  
36) Rossi B et al Front Immunol., 2021.pdf

accesso aperto

Tipologia: Documento in Post-print
Licenza: Dominio pubblico
Dimensione 1.36 MB
Formato Adobe PDF
1.36 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1037041
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 21
  • ???jsp.display-item.citation.isi??? ND
social impact