the role of autophagy in systemic lupus erthymatosus

Abstract

The aetiology of Systemic Lupus Erythematosus (SLE), a chronic autoimmune disease that can affect every organ and tissue in the body, is unknown. However, complex interactions among genetic, environmental (such as infectious agents, ultraviolet light, drugs), and hormonal factors are likely to play a role. Human leukocyte antigen regulation, T- and B-cell signalling, Toll-like receptor/interferon signalling, nuclear factor-kB signalling, and immune complex clearance are a few immune system-related pathways that are primarily dysregulated in SLE pathogenesis. A lysosome-mediated catabolic process called autophagy allows cells to recycle nutrients and break down undesirable cytoplasmic components. Along with being involved in both innate and adaptive immune responses, autophagy is crucial for contacts with microorganisms, processing of antigens for MHC presentation, and the growth, survival, and proliferation of lymphocytes. Macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy are the three primary kinds of autophagy. The most often researched of them, known as autophagy in general, is macroautophagy. More than 100 loci related with SLE susceptibility have been found by hypothesis-free genome-wide association studies (GWAS). Five autophagy-related genes were found to be linked to SLE susceptibility using this method. These include ATG5, CLEC16A (C-type lectin domain containing 16A), DRAM1, CDKN1B (cyclin dependent kinase inhibitor 1B), and ATG16L2. These findings resoundingly confirmed the idea that autophagy is crucial to the genetic aetiology of SLE. Combining with additional follow-up investigations, it was shown that a number of variations in other autophagy-related genes, including ATG7, IRGM, LRRK2, MAP1LC3B, MTMR3, and APOL1, were linked to SLE susceptibility.