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Increased levels of circulating soluble CD226 in multiple sclerosis.

Saniya Kari1, Florence Bucciarelli1, Thibault Angles1

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Multiple Sclerosis (Houndmills, Basingstoke, England)
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PubMed
Summary

Soluble CD226 (sCD226) is elevated in multiple sclerosis (MS) and neuromyelitis optica (NMO), suggesting T-cell activation releases sCD226, potentially promoting neuroinflammation.

Keywords:
CD4+ T cellsMultiple sclerosisbiomarkerdendritic cellssoluble CD226

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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.