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Updated: May 16, 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
Development of experimental autoimmune encephalomyelitis critically depends on CD137 ligand signaling
Julia M Martínez Gómez1, J Ludovic Croxford, Kim Pin Yeo
1Departments of Microbiology and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599.
Abstract:
Multiple sclerosis (MS) is a degenerative autoimmune disease of the CNS. Experimental autoimmune encephalomyelitis (EAE) is a commonly used murine model for MS. Here we report that CD137 ligand (CD137L, 4-1BB ligand, TNFS9), a member of the TNF superfamily, is critical for the development of EAE. EAE symptoms were significantly ameliorated in CD137L(-/-) mice. In the absence of CD137L, myelin oligodendrocyte glycoprotein (MOG)-specific T-cells secreted lower levels of T(h)1/T(h)17 cell-associated cytokines. MOG-specific T-cells also trafficked less efficiently to the CNS in CD137L(-/-) mice, possibly as a consequence of reduced expression of vascular cell adhesion molecule-1 (VCAM-1), which regulates leukocyte extravasation. Thus, CD137L regulates many functions of MOG-specific T-cells that contribute to EAE and may represent a novel therapeutic target for the treatment of MS.
Insights
CD137 ligand (CD137L) is crucial for experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Its absence ameliorates EAE symptoms by reducing T-cell cytokine production and CNS infiltration.
Area of Science:
- Neuroimmunology
- Immunology
- Molecular and Cellular Biology
Background:
- Multiple sclerosis (MS) is a debilitating autoimmune disease affecting the central nervous system (CNS).
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS pathogenesis.
- Understanding the molecular mechanisms underlying EAE is crucial for developing effective MS therapies.
Purpose of the Study:
- To investigate the role of CD137 ligand (CD137L) in the development of EAE.
- To elucidate the impact of CD137L on T-cell responses and CNS infiltration in the context of EAE.
Main Methods:
- Utilized CD137L knockout (CD137L(-/-)) mice to model EAE.
- Analyzed myelin oligodendrocyte glycoprotein (MOG)-specific T-cell responses, including cytokine production.
- Assessed T-cell trafficking to the CNS and expression of vascular cell adhesion molecule-1 (VCAM-1).
Main Results:
- EAE symptoms were significantly reduced in CD137L(-/-) mice compared to wild-type controls.
- MOG-specific T-cells from CD137L(-/-) mice exhibited decreased secretion of T(h)1/T(h)17 associated cytokines.
- Reduced CNS infiltration of MOG-specific T-cells was observed in CD137L(-/-) mice, correlated with lower VCAM-1 expression.
Conclusions:
- CD137 ligand plays a critical role in regulating T-cell functions essential for EAE development.
- CD137L influences T-cell cytokine production, CNS trafficking, and VCAM-1 expression.
- Targeting CD137L may offer a novel therapeutic strategy for treating multiple sclerosis.
