Sex-specific regulation of immune responses by PPARs

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. The sex-specific regulation of nuclear receptors in immune cells offers clues for treating diseases that affect men and women differently. Females tend to generate stronger immune responses than males. Although a clear advantage when fighting infections, stronger responses increase the risk of the immune system attacking the body's own tissues and cells – leading to autoimmune disease. Je-Min Choi and Hong-Jai Park at Hanyang University in Seoul, South Korea, review existing evidence of the sex-specific regulation of a family of nuclear receptors known as peroxisome proliferator-activated receptors (PPARs). Despite being best known for their roles in the regulation of metabolism, PPARs have the ability to dampen the immune response. Sex hormones influence the expression of PPARs in immune cells and could therefore be co-administered with PPAR-activating compounds to improve the treatment of autoimmune disease.