Fate mapping of IL-17-producing T cells in inflammatory responses

Although in vitro–generated cells of the TH17 helper T cell subset are highly plastic, it is unclear whether TH17 cells that develop in vivo retain their phenotype. To investigate this, Stockinger and colleagues have generated a TH17 reporter system to map the fate of these cells in vivo. Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (TH17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in TH17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of TH17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-TH17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to TH17 developmental origin regardless of IL-17 expression.