Journal
MOLECULAR NEURODEGENERATION
Volume 15, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13024-020-00375-7
Keywords
Regulatory T cells (Tregs); Effector T cells (Teffs); Dendritic cells; Microglia; Immune transformation; Neurodegenerative disorders
Categories
Funding
- National Institutes of Health [P01 DA028555, R01 NS36126, P01 NS31492, P01 MH64570, P01 NS43985, P30 MH062261, R01 AG043540, 2R01 NS034239]
- Frances and Louie Blumkin Research Foundation
- Harriet Singer Research Foundation
- Carol Swarts, MD Emerging Neuroscience Research Laboratory
- Margaret R. Larson Professorship
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Emerging evidence demonstrates that adaptive immunity influences the pathobiology of neurodegenerative disorders. Misfolded aggregated self-proteins can break immune tolerance leading to the induction of autoreactive effector T cells (Teffs) with associated decreases in anti-inflammatory neuroprotective regulatory T cells (Tregs). An imbalance between Teffs and Tregs leads to microglial activation, inflammation and neuronal injury. The cascade of such a disordered immunity includes the drainage of the aggregated protein antigens into cervical lymph nodes serving to amplify effector immune responses. Both preclinical and clinical studies demonstrate transformation of this altered immunity for therapeutic gain. We posit that the signs and symptoms of common neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke can be attenuated by boosting Treg activities.
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