Twisting the Th1/Th2 immune response via the retinoid X receptor: lessons from a genetic approach

The immune system is influenced by environmental factors such as hormones and nutrients. Previous studies have suggested that vitamins A and D influence the process of naive T helper (Th) cell differentiation into Th1 or Th2 cells. Vitamins A and D signal through the retinoid X receptor (RXR), which partners with either the retinoic acid receptor or the vitamin D receptor. Most previous studies into the role of RXR in Th differentiation have been performed in vitro and it was necessary for these to be verified in a physiological environment. However, in vivo study has been hindered since RXRalpha deficient mice are embryonic lethal. Du et al. in this issue of the European Journal of Immunology, overcome this obstacle using "pinkie" mice that harbor a hypomorphic mutation in the Rxralpha gene. The authors report that the mutant mice have an exaggerated Th1 immune response which is attributed to the aberrant antigen-presenting cell and CD4 T cell function. This study confirms previous studies indicating that RXR signaling plays an important role in Th cell differentiation and also provides a valuable tool with which to study the mechanisms and the in vivo functions of this signaling pathway.