Title:Suicidal emperipolesis: a process leading to cell-in-cell structures, T cell clearance and immune homeostasis.
Volume: 15
Issue: 9
Author(s): F. Sierro, S. S. Tay, A. Warren, D. G. Le Couteur, G. W. McCaughan, D. G. Bowen and P. Bertolino
Affiliation:
Keywords:
Autoimmunity, cell-in-cell, transplantation, CD8, tolerance, entosis.
Abstract: “Suicidal emperipolesis” is one of the most recently reported
processes leading to cell-in-cell structures that promote cell death. This
process was discovered in studies investigating the fate of autoreactive CD8 T
cells activated within the liver. Recently, we reported that activated T cells invaded hepatocytes, formed
transient cell-in-cell structures, and were rapidly degraded within endosomal/lysosomal compartments by a
non-apoptotic pathway. Importantly, pharmacological inhibition of this process caused intrahepatic
accumulation of tissue-reactive T cells and breach of immune tolerance. The characterization of the molecular
mechanisms of suicidal emperipolesis is still in its infancy, but initial studies suggest this phenomenon is
distinct from other reported cell-in-cell structures. As opposed to the formation of other cell-in-cell structures,
suicidal emperipolesis takes place in a non-malignant environment, and without obvious pathology. It is
therefore the first cell-in-cell structure described to have a role in maintaining homeostasis in normal
physiology in higher organisms. T cell emperipolesis within hepatocytes has also been observed by
pathologists in a range of chronic human liver pathologies. As T cell-in-hepatocyte structures resulting from
suicidal emperipolesis are very transiently observed in normal physiology, their accumulation during liver
disease would suggest that severe tissue injury is promoted by, or associated with, defective T cell clearance.
In this review, we compare “suicidal emperipolesis” to other processes leading to cell-in-cell structures, and
consider its potential biological roles in maintaining immune homeostasis and tolerance in the context of the
hepatic environment.
