Deletion of in a mouse model resulted in increased T-cell stimulation by DCs [102]. Autophagy Autophagy is a term derived from a Greek word meaning self-eating and is a process that together with the ubiquitin-proteasome system, governs the degradation of intracellular proteins. In addition to immunological functions, such as antigen presentation and protection against infection, autophagy is also involved in the starvation response, carcinogenesis, and quality control of intracellular proteins and is a constitutive process necessary for maintaining proper cell homeostasis and organ health [19,20,21]. In addition to IBD, autophagy INCB024360 analog has been shown to be associated with other diseases, such as asthma [22,23,24,25], systemic lupus erythematosus [26,27], and Parkinsons disease [28,29]. During the autophagy process, the endoplasmic reticulum or other membranous cellular structures respond to stimuli by generating a double-membrane structure called a phagophore. The ATG16L1/ATG5/ATG12 complex multimerizes and then lipidates light chain 3 (LC3)-II on this phagophore. Concurrently, the phagophore elongates to envelop the cytoplasm or organelle to be degraded, forming INCB024360 analog an autophagosome, which is a unique double-membrane organelle. The outer membrane of the autophagosome then integrates with a lysosome and forms an autolysosome. Finally, the inner membrane degrades and absorbs its contents [30] (Figure 2). Open in a separate window Figure 2 Autophagy mechanism. The endoplasmic reticulum or other membranous cellular structures respond to stimuli by generating a double-membrane structure called a phagophore. ATG16L1-ATG5-ATG12 complex multimerizes and then lipidates light chain 3 (LC3)-II on this phagophore. Concurrently, the phagophore elongates to envelop the cytoplasm or organelle to be degraded, forming an autophagosome. The outer membrane of the autophagosome then integrates with a lysosome and forms an autolysosome. Finally, the inner membrane degrades and absorbs its contents. 4. Role of Autophagy in Innate Immunity One of the functions of autophagy is control of the innate immune response. Many studies have revealed the involvement of autophagy in innate immune reactions, and extremely precise control mechanisms and pathophysiological roles are becoming more clearly understood and have begun to be elucidated [31,32]. 4.1. Xenophagy, Mitophagy Innate immunity is a mechanism through which almost all multicellular organisms protect themselves from pathogens. This pathway is activated when the constructive patterns of pathogens components are recognized (i.e., the cell wall components of a bacterial cell or the genome of a virus). Autophagy was initially thought to be a nonspecific mechanism for degrading substances by incorporating them into a membrane structure; however, recent studies have shown that autophagosomes selectively isolate a variety of substrates through sequestosome 1-like receptors, as is observed in autophagy of pathogens (xenophagy) [33,34,35]. Although the ubiquitin-proteasome system is a well-known selective intracellular degradation system, autophagy can selectively engulf and decompose small substances, such as mitochondria, which are larger than the focuses on of the ubiquitin-proteasome system, indicating characteristics related to that of mitophagy [36,37]. The major difference between autophagosomes and additional membranous organelles is definitely that autophagosomes have a dynamic structure in which necessary fractions are newly created and disappear with the digestion of material by fusion with lysosomes; as the necessity increases, as with the starvation state, its production effectiveness dramatically raises. These features are easy for quickly carrying INCB024360 analog out quantitative control, and even when IFNA-J functioning to control the immune response, autophagy is more suitable than degradation from the proteasome system, and it is believed to be essential for the resolution of quantitative problems. However, when autophagy works in connection with innate immunity, the substrates to be decomposed are hardly ever obvious except in the instances of xenophagy and mitophagy. 4.2. The Part of Autophagy in Inflammasomal and.
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