Researchers led by Ludwig Princeton’s Lydia Lynch reported in a Nature paper in October that innate IL-17-producing T cells—including γδ T cells, invariant natural killer T cells and mucosal-associated invariant T cells—express clock genes, which coordinate cellular physiology with the circadian cycle, at especially high levels. The immune system follows circadian rhythms to better combat potential infections, but these patterns have also been shown to be critical to its role in maintaining tissue health and integrity. Lydia and her team discovered that IL-17-producing γδ T cells, which reside in fat, rely on the molecular clock to maintain fat tissue homeostasis. These immune cells make the proinflammatory cytokines IL-17A and IL-17F in a rhythmic pattern that peaks at night, even in the absence of infection. They show that this is because rhythmic production of IL-17 is required to maintain fat metabolic rhythms, and that the cytokine is required for de novo lipogenesis—or the production of fat from sugar—in fat tissue. A lack of IL-17 disrupts circadian body temperature regulation (leaving mice cold) and the schedule on which sugars or fats are burned for energy. The findings of this study also have relevance for cancer, as mouse models that lack genes for IL17A/F have slower growing tumors. They suggest this could be due to IL-17’s influence on the lipid metabolism of tumor cells.
Rhythmic IL-17 production by γδ T cells maintains adipose de novo lipogenesis
Nature, 2024 October 30