Related Experiment Video
Updated: Aug 21, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
MMP-2 null mice exhibit an early onset and severe experimental autoimmune encephalomyelitis due to an increase in
Jordi Esparza1, Meghan Kruse, Janet Lee
1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Abstract:
Matrix metalloproteinase-2 (MMP-2; gelatinase A) is known to degrade a broad range of extracellular matrix components and chemokines, and has important roles in the processes of cell migration, invasion, and involution during development, as well as during tumor growth and metastasis and in inflammation and repair. To better elucidate the roles of this matrix metalloproteinase in the development and progression of experimental autoimmune encephalomyelitis, we used MMP-2-deficient (KO) mice. Surprisingly, we found that MMP-2 KO mice exhibited an earlier onset and more severe disease than did their wild-type (WT) counterparts. WT mice engrafted with MMP-2 KO bone marrow exhibited a similar earlier onset and more severe clinical disease score than WT mice engrafted with WT bone marrow. Lymphocytes derived from MMP-2 KO mice exhibited increased transmigration through endothelial cell monolayers as well as through collagen type IV and laminin-coated BD BIOCOAT inserts, which correlated with a 3-fold increase in expression of MMP-9 and was abrogated by inhibition of MMP activity. We demonstrated a correlation between expression levels of MMP-9 and MT1-MMP expression and suggest a signaling pathway involving tethering of MMP-2 to MT1-MMP as a modulator of MMP-9 expression. Last, we discuss other possible MMP-2-mediated mechanisms which may contribute to the observed phenotype.
Insights
Matrix metalloproteinase-2 (MMP-2) deficiency surprisingly worsens experimental autoimmune encephalomyelitis. MMP-2 knockout mice showed earlier, more severe disease, linked to increased MMP-9 expression and lymphocyte migration.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- Matrix metalloproteinase-2 (MMP-2) degrades extracellular matrix and influences cell migration.
- MMP-2 plays roles in development, tumor metastasis, inflammation, and repair.
Purpose of the Study:
- To investigate the role of MMP-2 in experimental autoimmune encephalomyelitis (EAE) development and progression.
- To understand MMP-2's specific contribution to autoimmune neuroinflammation.
Main Methods:
- Utilized MMP-2-deficient (KO) mice and wild-type (WT) littermates in an EAE model.
- Employed bone marrow transplantation studies to differentiate cell-intrinsic effects.
- Assessed lymphocyte transmigration across endothelial and basement membrane models.
- Measured MMP-9 and MT1-MMP expression levels.
Main Results:
- MMP-2 KO mice exhibited an earlier onset and more severe EAE than WT mice.
- Bone marrow chimeras showed similar exacerbated disease, indicating non-hematopoietic roles.
- MMP-2 deficiency led to increased lymphocyte transmigration, correlated with a 3-fold increase in MMP-9 expression.
- A correlation between MMP-9 and MT1-MMP expression was observed, suggesting a regulatory pathway.
Conclusions:
- MMP-2 deficiency exacerbates EAE, contrary to expectations.
- MMP-2 may normally act to suppress EAE severity, possibly by modulating MMP-9 activity.
- A signaling pathway involving MMP-2 tethered to MT1-MMP may regulate MMP-9 expression and influence neuroinflammation.
