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Peroxisome proliferator–activated receptor (PPAR) expression in T cells mediates gender differences in development of T cell–mediated autoimmunity

¹ Department of Neurology and Neurological Studies, and ² Department of Pathology, Stanford University Medical Center, Stanford, CA 94305
³ Department of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94143

CORRESPONDENCE Lawrence Steinman: steinman{at}stanford.edu

Peroxisome proliferator–activated receptor (PPAR) is a nuclear receptor that mediates gender differences in lipid metabolism. PPAR also functions to control inflammatory responses by repressing the activity of nuclear factor B (NF-B) and c-jun in immune cells. Because PPAR is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell–mediated autoimmune disease. We show that PPAR is more abundant in male as compared with female CD4⁺ cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-B and c-jun activity in male T lymphocytes, resulting in higher production of interferon and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPAR^–/– mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPAR.

Abbreviations used: CNS, central nervous system; DHT, 5-dihydroxytestosterone; EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; PPAR, peroxisome proliferator–activated receptor.

S.E. Dunn and S.S. Ousman contributed equally to this work.

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• Dunn, S. E., Ousman, S. S., Sobel, R. A., Zuniga, L., Baranzini, S. E., Youssef, S., Crowell, A., Loh, J., Oksenberg, J., Steinman, L. (2007). Peroxisome proliferator-activated receptor (PPAR){alpha} expression in T cells mediates gender differences in development of T cell-mediated autoimmunity. J. Cell Biol. 176: i9-i9 [Full Text]  

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