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

Cloning, identification and accurate normalization expression analysis of PPARα gene by GeNorm in Megalobrama amblycephala

“…But some studies also described that the deletion of PPARa had no apparent effect on the fertility of mice [43]. In addition, the difference of PPARa expression in different gonads was also gotten in T cells, because PPARa was found to be situated at the crossroads of gender and immune regulation, and it mediated gender differences in the development of T cell-mediated autoimmunity [44]. In this study, PPARa was more abundant in male as compared to female CD þ cells and its expression was sensitive to androgen levels.…”

“…In this study, PPARa was more abundant in male as compared to female CD þ cells and its expression was sensitive to androgen levels. This was due to the reason that males were less prone to develop Th1-mediated autoimmunity because they had higher T cell expression of PPARa [44].…”

Gender differences in the histopathology of MS?

“…This receptor is more abundant in male than in female CD4+ cells and ablation of the receptor results in higher IFNγ and TNFα and lower Th2 cytokine levels. Male mice lacking PPARα develop more severe EAE indicating that male sex protects against Th1-mediated autoimmunity [11]. Additionally, gender-specific, pro-inflammatory effects of IL-13 may contribute to increased susceptibility of females in EAE by upregulation of Th1-inducing cytokines [12].…”

Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms

“…For example, mice with a mutation knocking out one copy of the PPARg gene (PPARg +/À heterozygotes) [29], mice with a targeted disruption of the PPARg gene in macrophages (PPARg DMf ) [30], and mice that have a targeted disruption of the PPARg gene in the intestinal epithelium (PPARg DIEpC ) [31], all have increased susceptibility to chemically induced colitis. Similarly, mice that have both copies of the PPARa gene knocked out (PPARa À/ À homozygotes) have a worsened course of disease in several models for inflammatory and autoimmune disease, including chemically induced colitis [15], allergic asthma [32], carrageenan-induced edema and pleurisy [33], cerulein-induced pancreatitis [34], and EAE [35]. Remarkably, in all of these studies, a difference between control and PPAR-deficient mice in disease severity was observed in the absence of exogenously administered PPAR ligand, suggesting an anti-inflammatory role for either unliganded PPAR or PPAR bound to endogenous ligand(s).…”