PPARδ deficient mice develop elevated Th1/Th17 responses and prolonged experimental autoimmune encephalomyelitis
Saravanan Kanakasabai1, Crystal C Walline, Sharmistha Chakraborty
1Neuroscience Research Laboratory, Methodist Research Institute, Indianapolis, IN, USA.
Brain Research
|January 4, 2011
Summary
Peroxisome proliferator-activated receptor delta (PPARδ) deficiency in mice prolongs experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis. This suggests PPARδ is crucial for disease remission and recovery in EAE.
Area of Science:
- Neuroimmunology
- Molecular and Cellular Neuroscience
Background:
- Multiple sclerosis (MS) is a debilitating neurological disorder with unknown etiology and no cure.
- Peroxisome proliferator-activated receptor (PPAR) agonists have shown promise in ameliorating MS-like symptoms in experimental allergic encephalomyelitis (EAE).
Purpose of the Study:
- To investigate the physiological role of PPARδ in the regulation of central nervous system (CNS) EAE and MS.
- To determine the impact of PPARδ deficiency on EAE development, progression, and immune responses.
Main Methods:
- Utilized PPARδ deficient (PPARδ(-/-)) mice and wild-type (C57BL/6) control mice.
- Induced EAE in both groups and monitored disease onset, incidence, and severity.
- Analyzed immune cell populations and cytokine profiles (IFNγ, IL-17, IL-12p35, IL-12p40) in the brain and spleen.
Main Results:
- PPARδ(-/-) mice exhibited EAE with similar onset and incidence as wild-type mice.
- PPARδ(-/-) mice displayed prolonged EAE, with significant resistance to remission and recovery.
- Elevated levels of IFNγ, IL-17, IL-12p35, and IL-12p40 were observed in PPARδ(-/-) mice.
- Augmented Th1/Th17 responses and impaired Th2/Treg responses were noted in PPARδ(-/-) mice.
Conclusions:
- PPARδ(-/-) mice develop prolonged EAE, characterized by augmented Th1/Th17 responses.
- These findings highlight a critical physiological role for PPARδ in promoting remission and recovery from EAE.
- PPARδ signaling may represent a potential therapeutic target for managing MS.
