Decoding Cell Death: From a Veritable Library of Babel to Vade Mecum?

Abstract

Programmed cell death (PCD) is a requisite feature of development and homeostasis but can also be indicative of infections, injuries, and pathologies. In concordance with these heterogeneous contexts, an array of disparate effector responses occur downstream of cell death and its clearance—spanning tissue morphogenesis, homeostatic turnover, host defense, active dampening of inflammation, and tissue repair. This raises a fundamental question of how a single contextually appropriate response ensues after an event of PCD. To explore how complex inputs may together tailor the specificity of the resulting effector response, here we consider ( a) the varying contexts during which different cell death modalities are observed, ( b) the nature of the information that can be passed on by cell corpses, and ( c) the ways by which efferocyte populations synthesize signals from dying cells with those from the surrounding microenvironment.