Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis.

ABSTRACT: In colorectal cancer patients, a high density of cytotoxic CD8⁺ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8⁺ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8⁺ T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mit

SUBMITTER: Ziegler PK 

PROVIDER: S-EPMC6354256 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature