Autophagy Attenuates the Adaptive Immune Response by Destabilizing the Immunologic Synapse

Autophagy Enhances Intestinal Epithelial Tight Junction Barrier Function by Targeting Claudin-2 Protein Degradation

“…Emerging evidence shows autophagy to be a part of the complex pathogenesis of intestinal disorders. In particular, defective autophagy, leading to impaired immune responses, microbial sensing, destruction, and clearance, has been proposed to be a part of the pathogenesis of Crohn disease (12)(13)(14)(15). However, nothing is known about how autophagy regulates intestinal epithelial barrier function that act as the first line of host defense against intestinal luminal antigens and is an important component of innate immunity.…”

“…Among intestinal diseases, autophagy was first linked to pathogenesis of Crohn disease when genome-wide association studies identified mutations in the autophagy-related genes ATG16L1 and IRGM as risk factors for Crohn disease (9 -11). Recent studies have shown the role of autophagy in dendriticepithelial cell interactions, adaptive immune response, NOD2-directed bacterial sensing, lysosomal destruction, and immunemediated clearance to be important for the pathogenesis of IBD (12)(13)(14)(15). Although clinical data show a direct link between a defective intestinal TJ barrier and persistent and prolonged intestinal inflammation in IBD patients (5,16,17), the role of autophagy in the regulation of the intestinal epithelial TJ barrier remains unknown.…”

ATG16L1: A multifunctional susceptibility factor in Crohn disease

“…94 The altered function of ATG16L1-underexpressing dendritic cells causes stabilization of the interaction between dendritic cells and T cells, leading to an increased activation of T cells and T helper 17 cell responses characterizing the adaptive immune response in Crohn disease. 95 Loss-of-function of ATG16L1 or other autophagic proteins leads to the increased intramacrophagic replication of E. coli and to elevated secretion of pro-inflammatory cytokines, such as IL6 and TNF. 96 Moreover, in a recent study monocytes from patients with Crohn disease show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants, 97 which might give rise to an accumulation of bacterial products and an increased inflammatory reaction.…”

An asymmetrically dimethylarginated nuclear 90 kDa protein (p90aDMA) induced by interleukin (IL)-2, IL-4 or IL-6 in the tumor microenvironment is selectively degraded by autophagy

“…2B and D). A growing body of evidence indicates that similar elimination of signaling molecules play key roles in autophagy-regulated immune responses (53)(54)(55)(56)(57). For instance, microglial autophagy plays an important role in the clearance of extracellular Aβ (β-amyloid) fibrils and the regulation of Aβ-induced inflammation, thereby affecting neuronal viability (53).…”