Issues

CAFs are prominent members of the TME. Kuhn et al. demonstrate how local gene editing of CAFs alters their cell state and, subsequently, the cellular TME. This approach demonstrates a method to investigate intercellular circuits using targeted genetic perturbations in CAFs.

Wetterwald, Köck et al. report the existence of an endothelial metabolic checkpoint where MYCT1 restricts activity of IFITM2/3 to prevent energy waste at the vascular barrier and enable fat storage. This mechanism links endothelial nutrient handling to systemic energy balance, opening new directions for tackling obesity and metabolic disease.

CDN are second messengers that trigger type I IFN responses. Vila et al. show that DNA-PKcs, a major DNA damage response actor, directly interacts with CDNs through its kinase domain, ensuring CDN-associated signal termination, while CDNs inhibit DNA-PKcs catalytic activity.

Wetternwald and colleagues show that endothelial cells actively regulate energy storage in white adipose tissue through MYCT1–IFITM2/3-dependent control of endolysosomal trafficking and mTORC1 signaling. By limiting their own nutrient consumption, endothelial cells influence systemic energy partitioning, redefining the vasculature as a metabolic gatekeeper rather than a passive conduit.