771B Poster - 12. Physiology, metabolism and aging
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Rihab Loudhaief; Christian Christensen; Julien Colombani; Ditte Andersen

Affiliation: University of Copenhagen

Keywords:
j. physiology of adult organs; c. innate immunity

The family of tumor necrosis factors (TNFs) are implicated in diverse processes ranging from cell proliferation, differentiation and apoptosis to innate and adaptive immunity. While TNFs contribute to tissue homeostasis and immunity, they are also notorious for their pathological roles in promoting tumor growth and inflammatory diseases. In addition to their well-described pro-inflammatory functions, an increasing body of evidence suggest that TNF signaling plays an instrumental role in orchestrating the metabolic­­­ rewiring associated with disease conditions in both flies and mammals. While this suggests that TNF can act as a metabolic hormone, it is not known whether TNF-TNFR signaling regulates to metabolic processes in healthy individuals. Here we show that the fly TNF receptor (TNFR), Wengen (Wgn), localizes in intracellular vesicles in the adult fly gut and plays an important role in controlling lipid metabolism, tissue homeostasis and immunity. Knocking down Wgn in enterocytes (ECs) results in activation of autophagy, degradation of lipids, and increased sensitivity to starvation. Moreover, wgn mutant guts display ectopic activation of JNK/MAPK and IMD signaling causing accelerated epithelial turnover and increased immune activity. We further show that all these effects are ligand-independent and mediated by TNF associated factor (TRAF)3, as Wgn is required to restrict cytoplasmic levels of TRAF3. These findings suggest that in addition to previously reported pathological roles of TNF-TNFR signaling in promoting inflammation and disrupting energy homeostasis, TNFRs are crucial mediators of metabolism and tissue homeostasis and moderators of immunity in healthy organisms.