The immune system's challenge: The timely resolution of immune activity and resumption of homeostasis

The complete resolution of an immune response is the prerequisite for the return to homeostasis. Environmental factors and genetic variation add to the challenge of safely distinguishing minute residual amounts of pathogen in the context of abundant immune-mediated damage. The risk of a vicious circle in which damage-associated molecules drive a feed-forward, non-attenuating inflammatory response is inherent to this phase of the response.

Here, we study the circuit regulation of resolution and sensing in two key areas: cerebral innate immune activation in normal aging, neurodegeneration and regeneration, and modeling of tumor immune evasion and host restraints.