GPR109A is a receptor for the SCFA butylate. Previous work demonstrated that GPR109A is essential for butyrate-mediated induction of IL-18 in the intestinal epithelium, which facilitates repair of damaged tissue and then maintains gut homeostasis and regulates immune responses (left panel).^2,3 In addition, activation of GPR109A in colonic APCs, such as DCs, promotes anti-inflammatory responses (middle panel).^2,3 Docampo and colleagues have now clarified the role of GPR109A in allogeneic T cells, which enhance their inflammatory capacity in a butyrate-independent manner (right panel). Contrary to previous findings^2,3 in gut epithelial cells and APCs, this study demonstrates a novel intrinsic mechanism in allogeneic T cells that is mediated by GPR109A.