Tonic TNF conditioning of macrophages safeguards stimulus-specific inflammatory responses.

ABSTRACT: Tumor necrosis factor (TNF) is a key inflammatory cytokine that warns recipient cells of a nearby infection or tissue damage. Acute exposure to TNF activates characteristic oscillatory dynamics of the transcription factor NFκB and induces a characteristic gene expression program; these are distinct from the responses of cells directly exposed to pathogen-associated molecular patterns (PAMPs). Here, we report that tonic TNF exposure is critical for safeguarding TNF's specific functions. In the absence of tonic TNF conditioning, acute exposure to TNF causes (i) NFκB signaling dynamics that are less oscillatory and more like PAMP-responsive NFκB dynamics, (ii) immune gene expression that is more similar to the Pam3CSK4 response program, and (iii) broader epigenomic reprogramming that is chara

SUBMITTER: Luecke S 

PROVIDER: S-EPMC10328066 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature