Differential Regulation of CD4 T Helper Cell Subset Responses by 15- deoxy-Δ-Prostaglandin J in Experimental Autoimmune Encephalomyelitis

ABSTRACT

Peroxisome proliferator-activated receptor (PPAR) is a family of nuclear receptor transcription factors that regulates immune cell growth, differentiation and homeostasis. We and others have shown earlier that in vivo treatment with PPARα, β/δ or γ agonists ameliorates experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). In this study we show that C57BL/6 mice induced to develop EAE display augmented neural antigen-specific T cell response that was inhibited by PPARγ agonist 15-deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2). EAE mice showed elevated expression of IFNγ and IL-17 in the CNS and lymphoid organs compared to naive mice that decreased significantly following treatment with 15d-PGJ2. EAE mice also expressed elevated levels of IL-12 and IL-23 that decreased after treatment with 15d-PGJ2. 15d-PGJ2 also attenuated the expression of IFNγ, IL-17, IL-12 and IL-23 in neural antigenspecific spleen cells ex vivo and in vitro. Moreover, EAE mice expressed low levels of IL-4, IL-10 and PPARβ compared to naïve that increased significantly following treatment with 15d-PGJ2. However, 15d-PGJ2 failed to change the expansion of CD4+CD25+Foxp3+ Treg cells in EAE. These findings suggest that 15d-PGJ2 differentially regulates CD4+ T helper cell subset responses in EAE.

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