Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis.
Paul K Ziegler, Julia Bollrath, Charles K Pallangyo, Takaji Matsutani, Özge Canli, Tiago De Oliveira, Michaela A Diamanti, Nina Müller, Jaba Gamrekelashvili, Tracy Putoczki, David Horst, Arun K Mankan, Meryem G Öner, Susanna Müller, Josef Müller-Höcker, Thomas Kirchner, Julia Slotta-Huspenina, M Mark Taketo, Thomas Reinheckel, Stefan Dröse Show all
Cell | Published : 2018
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. ..View full abstract
Awarded by Intramural NIH HHS