Sick animals often lose their appetites. Though this behavior is widely observed across species, its consequences on the effector T cells battling infection was not clear. In a December paper in the Proceedings of the National Academy of Sciences, Ludwig MSK Director Alexander Rudensky and colleagues showed that starvation during infection decreases the number of effector T cells in mice through mechanisms governed by the cells’ Farnesoid X Receptor (FXR), a nuclear receptor also involved in liver responses to fasting and refeeding. That loss of effector T cells, they showed, could be reversed by the provision of the sugar glucose, supporting the sugar’s availability as a determinant of effector T cell survival. Deletion of FXR in T cells prevented their loss during starvation, altered their utilization of fuel from glucose to other nutrients and improved their fitness. It also caused weight loss in the mice. The study, supported by the Ludwig-Hilton Cancer Prevention Initiative, identified a mechanism by which the host scales immune responses in reaction to nutrient availability, and showed that FXR is the sensor in T cells that triggers those responses.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).