A TBC1D9-Rab29 axis controls homeostatic NF-κB signaling and selective IL-6 production in epithelial cells.

ABSTRACT:

Background

Interleukin-6 (IL-6) plays a crucial role in inflammation and immune defense; however, its intracellular trafficking and the mechanisms regulating its expression remain poorly understood.

Methods

We investigated epithelial cell responses to poly(dA:dT) stimulation and group A Streptococcus infection, using depletion and overexpression assays, NF-κB readouts, proteomics, co-immunoprecipitation, immunofluorescence imaging, and analysis of necrotizing soft tissue infection transcriptomes.

Results

TBC1D9, a Rab GTPase-activating protein, selectively regulates IL-6: its depletion reduced IL-6 mRNA and protein levels without broadly affecting other pro-inflammatory cytokines. TBC1D9 maintained basal p65 phosphorylation but was dispensable for stimulus-indu

SUBMITTER: Hu X 

PROVIDER: S-EPMC12643979 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature