LAUSR

TNF is generally believed to be a master pro-inflammatory cytokine, and anti-TNF therapy has become the mainstream treatment for some autoimmune diseases. However, experimental evidence indicates that TNF preferentially activates Tregs, resulting in their proliferation, and enhancing their phenotypic stability and suppressive capacity. This effect of TNF is mediated by the cell surface receptor TNFR2, which is highly expressed by both human and mouse Tregs (1–4). Furthermore, within Tregs, expression of TNFR2 identifies the most suppressive fraction of cells (5). This Research Topic summarizes the latest knowledge on the critical role that TNF-TNFR2 signaling play in modulating the biology of Tregs, as well as other immune-suppressive cell types. Moreover, it analyzes its implications in controlling harmful inflammatory responses, as well as the potential targeting of this key signaling pathway to develop new immunotherapies against cancer.