Ludwig MSK’s Alexander Rudensky and his team discovered in 2003 that the regulator of gene expression FOXP3 controls the induction and maintains the identity of regulatory T cells (Tregs). Tregs generally tamp down immune responses once an infection has been dealt with and are actively recruited by tumors to suppress anticancer immune responses. Genetic disabling of FoxP3 leads to fatal autoimmunity in mice, characterized by every known type of inflammatory response, all stemming from the loss of Tregs. But it has long been unclear whether Tregs can persist and effectively exert their function in a disease state, in which their activity is compromised or their target immune cells have become impervious to their influence. In a study published in the August issue of Nature Immunology, Alexander and postdoc Wei Hu showed that Tregs can indeed persist and function in diseased states. They engineered Foxp3-deficient mice capable of restoration of FoxP3 expression and Treg function on demand and showed that the aberrant immune activation and severe autoimmune disease could be efficiently and durably reversed by Treg cells and that a single pool of Tregs can provide long-term protection against inflammation and autoimmunity.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).