CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

Area of Science:

• Immunology
• Cell Biology
• Neuroscience

Background:

• Multiple sclerosis (MS) is an autoimmune disease characterized by T cell infiltration into the central nervous system.
• Elevated T cell adhesion is a hallmark of MS pathology.
• The cytoplasmic binding partner of fragile X protein (CYFIP2) role in T cell adhesion is not well understood.

Purpose of the Study:

• To investigate the role of CYFIP2 in T cell adhesion in multiple sclerosis patients.
• To determine if elevated CYFIP2 levels contribute to increased T cell adhesion in MS.

Main Methods:

• DNA microarray and Western blot analysis of CD4(+) and CD8(+) T cells from MS patients and controls.
• Adenoviral-mediated overexpression and antisense oligodeoxynucleotide-mediated knockdown of CYFIP2 in Jurkat and primary T cells.
• Assessment of fibronectin-mediated cell adhesion.
• Inhibition of Rac-1 activity.

Main Results:

• CYFIP2 protein levels were significantly increased in CD4(+) T cells from MS patients compared to healthy controls and IBD patients.
• Overexpression of CYFIP2 enhanced fibronectin-mediated adhesion in Jurkat cells.
• CYFIP2 knockdown reduced fibronectin-mediated adhesion in Jurkat and primary CD4(+) T cells.
• Inhibition of Rac-1, a CYFIP2 binding partner, reduced fibronectin-mediated adhesion in both cell types.
• Reducing CYFIP2 or inhibiting Rac-1 normalized T cell adhesion in MS patients.

Conclusions:

• Elevated CYFIP2 levels in T cells contribute to increased cell adhesion in multiple sclerosis.
• CYFIP2-mediated enhancement of T cell adhesion may be a therapeutic target for MS.