Deadline for manuscript submissions: 30 September 2025.
Aging has been associated with an increase in the expression of MHC class I molecules (MHC-I, HLA-I in humans, and H-2 in mice) in the brain, a process linked to synaptic pruning and neurodegeneration. However, several studies have also suggested a role for MHC-I molecules in neuroregeneration. Chronic low-grade inflammation is a common feature of the aging brain and is related to cognitive decline. In Alzheimer's and Parkinson's diseases, increased expression of MHC-I molecules in the brain parenchyma (e.g., microglia, endothelial cells, neurons, etc.) has been associated with dysregulation of brain homeostasis and cognitive decline. Interestingly, certain HLA-I genes/alleles, such as HLA-A2, HLA-A23, HLA-A24, HLA-B7, and HLA-B8, are associated with neurodegeneration. In contrast, others, such as HLA-B40 and HLA-C03, confer protection, suggesting a common role for MHC-I molecules in fine-tuning the equilibrium between neurodegeneration and neuroregeneration.
In this special issue of Immune Discovery, we invite you to contribute original research articles, reviews, case reports, or expert perspectives and/or opinions on all aspects related to "MHC Class I Research in Aging and Brain Homeostasis (ABH)."
Relevant topics related to ABH might include:
As mankind breaks the boundaries of potential years to live, the process of aging imposes various cellular challenges, from less capacity of cell repair and damage to impaired protein formation, causing chronic low-level inflammation on tissues including the brain. Persistent chronic neuroinflammation can harm neurons, contributing to the development of neurodegeneration, a pathological process that affects cognitive function and is often reflected by dementia. This opinion article tries to recapitulate the influence that major histocompatibility class I (MHC-I) molecules have on brain homeostasis and how abnormalities in their expression can lead to cognitive deterioration. Studies carried out during recent years not only demonstrated that neurons and other central nervous system (CNS) cells express MHC-I molecules, but also that these molecules play essential roles in the establishment, function, and modeling of synapses in the CNS during the embryonic period, at birth and during adulthood, namely during inflammatory conditions. The accumulated body of evidence suggests that MHC-I molecules and the signaling pathways they regulate could provide clues on some of the molecular and cellular mechanisms regulating brain homeostasis and neuroregeneration in health and disease, thus becoming potential biomarkers of cognitive decline and targets for innovative immunotherapies.
