J Immunol. 2003 Dec 1;171(11):5743-50
Bright JJ, Natarajan C, Muthian G, Barak Y, Evans RM.
Departments of Neurology and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212. Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor transcription factor that regulates cell growth, differentiation, and homeostasis.
PPARgamma agonists are potent therapeutic agents for type 2 diabetes, obesity, and inflammation.
Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model of multiple sclerosis.
We have shown recently that PPARgamma agonists inhibit EAE by blocking IL-12 production, IL-12 signaling, and neural Ag-induced Th1 differentiation.
In this study, we show that the PPARgamma-deficient heterozygous mice develop an exacerbated EAE with prolonged clinical symptoms than the wild-type littermates, following immunization with myelin oligodendrocyte glycoprotein (MOG) p35-55 peptide.
The exacerbation of EAE in PPARgamma(+/-) mice associates with an increased expansion of CD4(+) and CD8(+) T cells and expression of CD40 and MHC class II molecules in response to MOGp35-55 Ag.
The PPARgamma(+/-) mice also showed an increase in T cell proliferation and Th1 response to MOGp35-55 Ag than the wild-type littermates.
These findings suggest that PPARgamma be a critical physiological regulator of CNS inflammation and demyelination in EAE and perhaps multiple sclerosis and other Th1 cell-mediated autoimmune diseases.