Evolved to protect, designed to destroy: IL-17-producing γδ T cells in infection, inflammation, and cancer

T cells of the gamma delta (gamma delta) lineage are evolutionary conserved from jawless to carti-laginous and bony fish to mammals and represent the "swiss army knife" of the immune system capable of antigen-dependent or independent responses, memory, antigen presentation, regulation of other lymphocytes, tissue homeostasis, and mucosal barrier maintenance, to list a few. Over the last 10 years, gamma delta T cells that produce the cytokine IL-17 (gamma delta T17) have taken a leading position in our understanding of how our immune system battles infection, inflicts tissue damage during inflammation, and gets rewired by the tumor microenvironment. A lot of what we know about gamma delta T17 cells stems from mouse models, however, increasing evidence implicates these cells in numerous human diseases. Herein, we aim to give an overview of the most common mouse models that have been used to study the role of gamma delta T17 cells in infection, inflammation, and cancer, while at the same time we will evaluate evidence for their importance in humans. We hope and believe that in the next 10 years, means to take advantage of the protective and destructive properties of gamma delta T and in particular gamma delta T17 cells will be part of our standard immunotherapy toolkit.