Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Enzyme Function
• Blood-Brain Barrier Research

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS).
• Matrix metalloproteinase-9 (MMP-9) is implicated in EAE, but the roles of other MMPs, such as matrilysin/MMP-7, are unclear.
• MMP-7 can degrade proteins crucial for blood-brain barrier integrity and immune suppression.

Purpose of the Study:

• To investigate the role of matrilysin/MMP-7 in the development of EAE.
• To determine if MMP-7 is a potential therapeutic target for multiple sclerosis.

Main Methods:

• Induction of EAE in wild-type and MMP-7-deficient mice using myelin oligodendrocyte glycoprotein (MOG).
• Assessment of immune cell infiltration in the central nervous system (CNS) via brain section analysis.
• Analysis of MOG-specific splenocyte proliferation and immune cell populations (CD4+, CD8+).
• Adoptive transfer experiments to assess the role of splenocytes and lymphocytes.
• In vitro blood-brain barrier model to evaluate the effect of recombinant MMP-7 on endothelial cell permeability.

Main Results:

• MMP-7-deficient mice were resistant to MOG-induced EAE, showing no significant immune cell infiltration in the CNS.
• Wild-type mice exhibited extensive vascular cuffing and mononuclear cell infiltration, with MMP-7-expressing cells found in vascular cuffs.
• MOG-specific immune cell proliferation was reduced in MMP-7-deficient mice.
• Adoptive transfer of MMP-7-deficient cells did not induce EAE in naive recipients, while wild-type cells did.
• Recombinant MMP-7 increased endothelial cell permeability in an in vitro blood-brain barrier model.

Conclusions:

• MMP-7 plays a critical role in facilitating immune cell access and/or re-stimulation in perivascular areas during EAE.
• These findings highlight MMP-7 as a potential therapeutic target for treating multiple sclerosis.