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Abstract

manifestations, such as lupus nephritis (1). To date, a clear pathogenesis of SLE has not been fully elucidated. Therefore, searching for the mechanisms involved in the development of SLE and targeting potential mechanisms for treatment remain topics of investigation.Absent in Melanoma 2 (AIM2) is a member of the pyrin and hematopoietic interferon (IFN)-inducible nuclear domain proteins. This protein has wide-ranging, propyroptotic properties. Regarding innate immunity, AIM2 serves as a cytoplasmic double-stranded DNA (dsDNA) sensor, regulating the initiation of innate immune responses (2). The recognition of dsDNA by AIM2 results in the assembly of a large multiprotein oligomeric complex known as the inflammasome, which regulates interleukin-1β (IL-1β) and IL-18 generation and induces cell death. In the cytosol, sensing of dsDNA by AIM2 is important for protection against invading pathogens, such as bacteria, viruses, and fungi. Conversely, the response of AIM2 to dsDNA released by damaged host cells may lead to the production of different cytokines that are involved in the pathogenesis of sterile inflammatory diseases, such as skin and kidney diseases. AIM2 contributes to lung tumorigenesis through the inflammasomedependent release of IL-1β and the regulation of mitochondrial dynamics. The AIM2 inflammasome becomes activated in the presence of atherosclerotic plaque, abdominal wall aortic aneurysm, and injured myocardium.To date, the findings of studies on AIM2 in the setting of lupus have been inconsistent. In a recent study by Dr. Lu and colleagues (1), it was found that Aim2 gene-deficient mice developed lupus, demonstrated by high histologic scores and high serum levels of dsDNA, myeloperoxidase, proteinase 3, albumin, and urea nitrogen, after pristane treatment. Increased infiltration of dendritic cells, macrophages, neutrophils, B cells, and T cells as well as high type I IFN signatures were also found in the kidneys of Aim2 gene-deficient mice treated with pristane. Aim2 deficiency resulted in elevated expression of type I IFN-induced genes in the kidneys, suggesting that AIM2 inhibits the development of lupus (1).Similarly, Panchanathan et al predicted that Aim2 deficiency contributed to increased susceptibility to lupus (2). In their study, Aim2 gene-deficient mice had high expression of p202 protein, which correlated with increased expression of IFNβ, STAT1, and IFN-inducible genes (2). In contrast, Huang et al evaluated Aim2 expression in lupus nephritis patients and found that Aim2 was highly expressed in the glomerular cells of patients with lupus nephritis class II (3).Yang et al found that in SLE patients, Aim2 expression was increased in germinal center B cells and plasma cells from peripheral blood, and in tonsil memory and skin lesions (4). Proportions of CD19+ cells were down-regulated in the lymph nodes and spleens of mice with lupus and Aim2 gene-deficient B cells. Aim2 deficiency in B cells attenuated the development of lupus, as shown by reduced glomerulonephritis, lower proportions of LE...