Genetic control of autophagy underlies pathogenesis of inflammatory bowel disease

Abstract

Autophagy contributes to cellular homeostasis in the face of nutrient deprivation and other cellular stresses. Cell type-specific functions for autophagy are critical in maintaining homeostasis at both the tissue level and at the whole-organism level. Recent work has highlighted the ways in which human genetic variants modulate autophagy to alter epithelial and immune responses in inflammatory bowel disease.

Figure 1.. Pleiotropic effects of autophagy in the intestine

Non-selective or bulk autophagy underlies cellular homeostasis in the intestine. Additionally, perturbations to non-canonical autophagy and cargo-selective autophagy result in cell type-specific alterations. This schematic illustrates how disruptions to autophagy, selective autophagy, or non-canonical autophagy can impact intestinal epithelial cells as well as both innate and adaptive immune cells. Furthermore, it is likely that autophagy controls the differentiation of rare cell types that have yet to be defined.