Single-cell profiling reveals periventricular CD56^bright NK cell accumulation in multiple sclerosis

Area of Science:

• Neuroimmunology
• Cellular immunology
• Single-cell analysis

Background:

• Multiple sclerosis (MS) is a chronic demyelinating disease involving immune cell infiltration in the brain, primarily affecting periventricular areas.
• Previous research on MS pathogenesis has focused on specific immune cell populations, neglecting a comprehensive analysis of all immune cells, including natural killer (NK) cells.

Purpose of the Study:

• To perform a full-spectrum analysis of the immune landscape in the brain's periventricular regions and circulation of individuals with MS, dementia, and controls.
• To identify novel immune cell signatures associated with MS, particularly focusing on natural killer (NK) cells.

Main Methods:

• Single-cell mass cytometry (CyTOF) was employed using a 37-marker panel to profile immune cells.
• Samples analyzed included brain periventricular areas (septum and choroid plexus) and peripheral blood from donors with MS, dementia, and neurological disease-free controls.
• Multiplex immunohistochemistry was used for validation.

Main Results:

• The study revealed the infiltration of T cells and antibody-secreting cells in the periventricular brain regions of MS patients.
• A novel NK cell signature specific to MS was identified, characterized by the accumulation of CD56^bright NK cells in the septum.
• These CD56^bright NK cells exhibited an activated and migratory phenotype, consistent with circulating counterparts, and were increased in periventricular lesions and choroid plexus in MS.

Conclusions:

• CD56^bright NK cells accumulate in the periventricular brain regions of multiple sclerosis patients.
• This accumulation suggests a significant role for NK cells in MS pathology, warranting further investigation.
• The findings bring NK cells into the spotlight of MS research.