Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease

Abstract

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed the contribution of autophagy to the innate immune response, and relationships between this process and various diseases have been reported. Inflammatory bowel disease is an intractable disorder with unknown etiology; however, immunological abnormalities in the intestines are known to be involved in the pathology of inflammatory bowel disease, as is dysfunction of autophagy. In Crohn’s disease, many associations with autophagy-related genes, such as ATG16L1, IRGM, NOD2, and others, have been reported. Abnormalities in the ATG16L1 gene, in particular, have been reported to cause autophagic dysfunction, resulting in enhanced production of inflammatory cytokines by macrophages as well as abnormal function of Paneth cells, which are important in intestinal innate immunity. In this review, we provide an overview of the autophagy mechanism in innate immune cells in inflammatory bowel disease.

Oxyresveratrol Induces Autophagy via the ER Stress Signaling Pathway, and Oxyresveratrol-Induced Autophagy Stimulates MUC2 Synthesis in Human Goblet Cells

“…Mucin is known as the major component in the intestinal mucus layer, and the intestinal mucosal barrier plays a critical role in maintaining intestinal homeostasis and preventing external damage. Autophagy promotes expression of MUC2 [19,50,51], and OXY induces MUC2 expression in intestinal goblet cells [17]. In this study, we found that OXY activates autophagy and that OXY-induced MUC2 expression is decreased by an ER inhibitor.…”

GPA Peptide-Induced Nur77 Localization at Mitochondria Inhibits Inflammation and Oxidative Stress through Activating Autophagy in the Intestine

“…In HepG2 cells, it was demonstrated that celastrol promotes Nur77 ubiquitination and induces its translocation to mitochondria, resulting in induction of autophagy and suppression of inflammation [21]. Meanwhile, autophagy represents an effective way to control inflammatory responses and oxidative stress [42,[61][62][63][64][65][66]. In our study, we found that GPA treatment promotes Nur77 translocation from the nucleus to mitochondria, then enhancing Nur77 interaction with TRAF6 and p62 to induce autophagy, resulting in suppression inflammatory and oxidative stress.…”

Interaction between HuR and circPABPN1 Modulates Autophagy in the Intestinal Epithelium by Altering ATG16L1 Translation

“…Although most members of this microbial community perform beneficial functions, certain pathogenic bacteria can evade this defense barrier and enter intestinal epithelial cells (IECs) (4). IEC-intrinsic innate immune responses limit bacterial invasion and maintain beneficial host-bacterium relationships (5,6), but the cellular processes that control intestinal epithelial interactions with invasive pathogens remain largely unknown. Autophagy is an evolutionarily conserved process in which cytoplasmic pathogens and unwanted components are targeted to the lysosome for degradation (7)(8)(9).…”