Autophagy and Inflammation

Abstract

The cellular degradative pathway of autophagy has a fundamental role in immunity. Here, we review the function of autophagy and autophagy proteins in inflammation. We discuss how the autophagy machinery controls the burden of infectious agents while simultaneously limiting inflammatory pathologies, which often involves processes that are distinct from conventional autophagy. Among the newly emerging processes we describe are LC3-associated phagocytosis and targeting by autophagy proteins, both of which require many of the same proteins that mediate conventional autophagy. We also discuss how autophagy contributes to differentiation of myeloid and lymphoid cell types, coordinates multicellular immunity, and facilitates memory responses. Together, these functions establish an intimate link between autophagy, mucosal immunity, and chronic inflammatory diseases. Finally, we offer our perspective on current challenges and barriers to translation.

A STING to inflammation and autoimmunity

“…Autophagy involves the transportation of the substrates present in the cytosol into the lysosomes through the formation of autophagosome, a double membrane‐bound vesicle intermediate involved in the process . In addition to its other homeostatic functions, autophagy is directly involved in the protective immune response by sequestering the intracellular pathogens by the process of xenophagy.…”

Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway

“…Basic fibroblast growth factor (bFGF) could promote the proliferation and migration of fibroblasts through the activation of Wnt/β‐catenin signalling pathway . Autophagy has been known as a conserved catabolism to sustain cellular homeostasis . It plays critical roles in eliminating dysfunctional or surplus proteins and damaged intracellular organelles .…”

cGAS, a DNA Sensor, Promotes Inflammatory Responses in Huntington Disease

“…Inflammation is also closely linked to autophagy, a process that is dysregulated in HD (23,24). Thus, inflammation is a prominent cellular response in HD patients and across various HD models, though the mechanisms remain less clear.…”

“…STING recruits TANK-binding kinase 1 (TBK1), which phosphorylates transcription factors such as interferon regulatory factor 3 (IRF3), interferon regulatory factor 7 (IRF7), and other substrates such as IκB kinase  (IKK), cRel, and p62 (sequestosome) (29,30). The cGAS synthase also plays a major role in the regulation of autophagy, suggesting a close molecular and signaling link between inflammatory response and autophagy (7,8,23,31). Despite a well-established role for cGAS in cancer, diabetes, and immune disorders, its role in neurodegenerative disease remains less clear (32)(33)(34).…”