Sorting out lysosomal trafficking of the thiazide-sensitive Na-Cl Co-transporter.

cells, are similarly present on some Tregs. As a result, Tregs home to the same regions in inflamed organs as their proinflammatory targets to control exuberant immune responses. This notion is suggested by several studies in the recent years13,14; however, Eller et al.1 did not find Tregs in inflamed kidneys of wild-type animals. This observation is surprising because it contradicts previous studies in other organs as well as our own unpublished data, which show regular presence of Tregs in kidneys of mice with NTS, and in various human renal pathologies. A possible explanation for this discrepancy is that numbers of infiltrating Tregs depend on the severity of disease, which was mild in the study by Eller et al.,1 a common issue with NTS in mice on the BALB/c background. Furthermore, modulation of an immune response by Tregs might follow a certain time course in which Tregs are first found in secondary lymphoid tissues and only then infiltrate inflamed target organs at later stages. The current study supports this latter hypothesis. Eller et al.1 show that Tregs have the potential to downregulate the immune response directly at the systemic site of antigen-specific T cell priming, namely the lymph node. Tregs are guided to this location, in analogy to activated dendritic or naive T helper cells, by the chemokine receptor CCR7. Thus, there are not only Tregs matching committed T cell lineages of the effector arm but also a population designed to monitor the activation of naive T cells. As a result, it is guaranteed that every step of a potentially hazardous T cell response, from priming within secondary lymphoid organs to damaging the parenchyma of target organs, is under the control of Tregs. The most common form of obsessivecompulsive disorder in humans, compulsive checking, therefore seems to be an issue for Tregs as well.