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Cell Immune system study of cerebrospinal fluid in aging population

 Last Update: 2022-12-30
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Neuroinflammation is one of the pathological hallmarks of aging-related neurodegenerative diseases [1].

The brain is surrounded by a layer of meninges, which contains a large amount of cerebrospinal fluid (CSF).

Under pathological conditions, the meningeal lymphatic system carries cerebrospinal fluid and the immune cells in it into deep cervical lymph nodes, allowing peripheral immune cells to contact brain antigens and initiate an immune response [2,3].

After peripheral T cells contact brain antigens, they can flow into the cerebrospinal fluid through the system circulation, which plays an immune surveillance role in the intrathecal space [4-7].

Mouse model studies have shown that choroid plexus, which produces cerebrospinal fluid, is also the site
of brain-circulatory interactions and age-related chronic neuroinflammation.
Recent studies have shown that cerebrospinal fluid alters the level
of its own myeloid cells by providing molecular information to immune cells in the bone marrow of the skull.
Of course, the molecular mechanism by which human aging regulates the immune response of cerebrospinal fluid is still not well understood
.
Moreover, it is inconclusive
whether changes in the cerebrospinal fluid immune system are associated with behavioral changes, such as cognitive impairment.

On December 13, 2022, David Gate's research group from Northwestern University published a report in Cell titled Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive Impairment's article, Exploring the CSF Immune System by Single-Cell Transcriptional Profiling and Finding that the CXCL16-CXCR6 signaling pathway guides CD8+ T cells into the CSF
.

Previous work by the authors' team noted that changes in the cerebrospinal fluid immune system are associated with pathological processes in aging-related neurodegenerative diseases such as Alzheimer's disease and dementia with Lewy bodies, therefore, It can be speculated that comparing the transcriptome changes of cerebrospinal fluid immune cells in people with normal cognition and cognitive impairment during aging can provide new clues
for the study of the pathological process of aging-related neuroinflammation in neurodegenerative diseases.
The authors collected cerebrospinal fluid samples from 45 cognitively normal older adults and performed single-cell RNA sequencing on these samples, ranging in age from 54 to 82 years
.
The authors found that with age, the lipid transporter genes of monocytes were significantly upregulated
.

Next, the authors used the above results as a control to compare
the results of single-cell RNA sequencing from 14 cerebrospinal fluid samples from cognitively impaired elderly adults.
The authors found that the downregulation of lipid transporter genes in monocytes occurred simultaneously with changes in the cytokine signaling pathway of CD8+ T cells in the case of cognitive impairment compared to controls
.
The level of CXCR6 (C-X-C motif chemokine receptor 6) in clonal and expanded CD8+ effector memory cells was significantly upregulated
.
CXCL16 (C-X-C MOTIF CHEMOKINE LIGAND 16) is a class of T cell chemokine and scavenger receptor for oxidized lipoprotein
。 CXCL16 levels in cerebrospinal fluid in older people with cognitive impairment are also elevated and are associated with
neural axis damage.
Moreover, the authors also determined from brain samples from Alzheimer's patients that CXCR6+ T cells and CXCL16+ myeloid cells
were localized in amyloid plaques.
Through the above single-cell sequencing and omics results, the authors determined that the CXCL16-CXCR6 signaling pathway is one of
the key conditions for T cells to enter the brain in the development and development of neurodegenerative diseases.

For Alzheimer's disease, the study of innate immune response is much deeper
than acquired immunity.
Alzheimer's disease high-risk genes identified through GWAS (genome-wide association studies) often also come from innate immune cells
.
Through the above single-cell sequencing results, the authors identified a group of genes with obvious changes in T cells in the cerebrospinal fluid of elderly people with cognitive impairment, which is also a group of Alzheimer's disease high-risk genes
.
The authors believe that most of the genes at high risk of Alzheimer's disease in cerebrospinal fluid are derived from acquired immune cells such as CD4+ and CD8+ T cells
.

In summary, the authors found that the cerebrospinal fluid immune system and cognitive impairment in cognitively normal older adults are clearly
different.
By detecting and analyzing changes in the immune system in cerebrospinal fluid, the correlation
between cognitive impairment in humans and disease-associated neuroinflammation was determined.

Original link:

https://doi.
org/10.
1016/j.
cell.
2022.
11.
019

Platemaker: Eleven

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