CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis.

Area of Science:

• Neuroimmunology
• Cellular and Molecular Medicine

Background:

• Phagocytes, including macrophages and microglia, are central to multiple sclerosis (MS) pathophysiology, driving neuroinflammation and neurodegeneration.
• Siglec-1 (CD169) is increasingly recognized as a marker for activated phagocytes in inflammatory conditions.

Purpose of the Study:

• To investigate the specific role of CD169-expressing phagocytes in MS-related neuroinflammation.
• To determine if CD169 can serve as a therapeutic target for MS.

Main Methods:

• Utilized CD169-diphtheria toxin receptor (DTR) mice for targeted depletion of CD169+ cells.
• Employed flow cytometry and immunohistochemistry to analyze CD169 expression and distribution in MS and EAE models.

Main Results:

• CD169 was highly expressed on lesional and circulating phagocytes in MS and experimental autoimmune encephalomyelitis (EAE).
• CD169 identified early-activated microglia in MS and EAE lesions.
• Depletion of CD169+ cells significantly reduced neuroinflammation and improved disease symptoms in EAE mice.

Conclusions:

• CD169+ cells are key drivers of neuroinflammation in MS.
• CD169+ phagocytes play a critical role in the disease's pathology.
• Targeting CD169+ phagocytes presents a promising therapeutic avenue for MS treatment.