Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis.
Cell-Division, Demyelinating-Diseases, Encephalomyelitis-Experimental-Autoimmune, Female, Glycoproteins, Heterozygote-Detection, Histocompatibility-Antigens-Class-II, Injections-Intramuscular, Interferon-Type-II, Interleukin-12, Lymphocyte-Activation, Mice-Inbred-C57BL, Mice-Knockout, Nerve-Tissue-Proteins, Peptide-Fragments, Peroxisomes, Receptors-Cytoplasmic-and-Nuclear, Severity-of-Illness-Index, Spleen, SUPPORT-U-S-GOVT-P-H-S, Th1-Cells, Transcription-Factors, Up-Regulation
J Immunol 2003 Dec; 171(11):5743-50.
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.
Bright, J J.; Natarajan, C; Muthian, G; Barak, Y; and Evans, R M., " Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis." (2003). Faculty Research 2000 - 2009. 681.