Increased levels of circulating soluble CD226 in multiple sclerosis

Area of Science:

• Immunology
• Neuroscience
• Biochemistry

Background:

• The glycoprotein CD226 is crucial for immune cell regulation.
• Soluble CD226 (sCD226) is elevated in chronic inflammatory diseases.
• sCD226 levels in neuroinflammatory diseases like multiple sclerosis (MS) remain unknown.

Purpose of the Study:

• Investigate sCD226 presence and functional roles in persons with MS (pwMS) and other neurological conditions.
• Determine if sCD226 is a potential biomarker for neuroinflammation.

Main Methods:

• Analyzed CD226 surface expression and T-cell supernatants to understand sCD226 production mechanisms.
• Assessed sCD226's impact on dendritic cell maturation.
• Measured sCD226 serum concentrations in healthy donors (HD), pwMS, neuromyelitis optica (NMO), and Alzheimer's disease (AD) patients.

Main Results:

• T-cell costimulation with CD3/CD226 induced CD226 shedding, releasing sCD226.
• sCD226 addition to maturing dendritic cells increased pro-inflammatory interleukin-23 (IL-23) production.
• Significantly elevated sCD226 levels were found in pwMS and NMO patients compared to HD and AD patients.
• MS patients, including relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS), showed increased sCD226 compared to clinically isolated syndrome (CIS).

Conclusions:

• T-cell activation releases sCD226, which may drive neuroinflammation.
• sCD226 presents potential as a biomarker for neuroinflammatory diseases like MS.