Sex-specific regulation of immune responses by PPARs

ABSTRACT

The prevalence of autoimmune, infectious and metabolic diseases is different for men and women owing to the respective ability of their immune systems to respond to self and foreign antigens. Although several factors, including hormones and the X-chromosome, have been suggested to contribute to such sex-specific immune responses, the underlying factors remain poorly defined. Recent studies using peroxisome proliferator-activated receptor (PPAR) ligands and knockout mice have identified sex-dimorphic expression of PPARs, and have shown that the inhibitory functions of PPAR in T cells are substantially affected by the sex hormones. In this review, we consider the sex-specific differences in PPARs and summarize the diverse PPAR-mediated, sex-specific properties of effector T-cell responses, such as T-cell activation, survival and differentiation, as well as their involvement in T-cell-related autoimmune diseases, including colitis, graft-versus-host disease and experimental autoimmune encephalomyelitis. Understanding PPAR-mediated sex differences in immune responses will provide more precise insights into the roles of PPARs in effector T cells.