Cell-autonomous epithelial activation of AIM2 (absent in melanoma-2) inflammasome by cytoplasmic DNA accumulations in primary Sjögren's syndrome

Vakrakou, Aigli G.; Svolaki, Ioanna; Evangelou, Konstantinos; Gorgoulis, Vassilis G.; Manoussakis, Menelaos N.

doi:10.1016/j.jaut.2019.102381

Cited by 33 publications

(28 citation statements)

References 51 publications

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“…Stimulation of the AIM2 inflammasome occurs follow ing binding by cytosolic free DNA (cfDNA) of viral, bac terial or mammalian origin, but not by other triggers 112 . Some data suggest that the AIM2 inflammasome is highly active in SGECs from patients with pSS, which could be because of defective functioning of DNase 1 resulting in the accumulation of cfDNA 113 . Patients with pSS and MALT lymphomas, and those patients with pSS judged to be at a high risk of developing MALT lympho mas, have high serum levels of cf DNA and extranuclear DNA accumulations in salivary gland tissue, mostly localized between the striated ducts and lymphocytic infiltrates 114 .…”

Section: The Inflammasomementioning

confidence: 99%

Epithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis

et al. 2021

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In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-κB pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4 + T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS.

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Section: The Inflammasomementioning

confidence: 99%

Epithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis

et al. 2021

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“…Early evidence has also been shown in other oral diseases, even though not much. The ductal salivary epithelia of primary Sjögren's syndrome patients display persistent AIM2 activation due to cytoplasmic accumulations of damaged DNA (69). A certain etiologic agent of dental caries, Streptococcus mutans, is capable of activating AIM2 inflammasome in THP-1 cells (70).…”

Section: Other Oral Diseasesmentioning

confidence: 99%

AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases

et al. 2020

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A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed inflammasomes, which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the "canonical" inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009-2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

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“…AIM2 sensing of self-DNA and the resulting inflammasome responses play critical roles in autoimmunity, chemotherapy-induced toxicity, and neurodevelopment and ASC specks have been observed in the ductal epithelia in SS patients. 76 Additionally, damaged genomic DNA colocalized with AIM2 in the specimens of SS patients but not controls. The low Dnase I expression in the salivary gland epithelial cell (SGEC) lines and the ductal tissues of SS patients implied that the defective cytosolic DNA degradation underlies AIM2 activation in SS.…”

Section: Autoimmune and Sterile Inflammatory Diseasesmentioning

confidence: 97%

AIM2 in health and disease: Inflammasome and beyond

Kumari

Russo

Shivcharan

et al. 2020

Immunological Reviews

121

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Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. A set of germline‐encoded innate immune receptors detect microbial DNA in various compartments of the cell, such as endosomes, the cytosol, and the nucleus. Sensing of microbial DNA through these receptors stimulates, in most cases, interferon regulatory factor‐dependent type I IFN synthesis followed by JAK/STAT‐dependent interferon‐stimulated gene expression. In contrast, the detection of DNA in the cytosol by AIM2 assembles a macromolecular complex called the inflammasome, which unleashes the proteolytic activity of a cysteine protease caspase‐1. Caspase‐1 cleaves and activates the pro‐inflammatory cytokines such as IL‐1β and IL‐18 and a pore‐forming protein, gasdermin D, which triggers pyroptosis, an inflammatory form of cell death. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasome‐dependent and inflammasome‐independent manners. This review discusses the latest advancements in our understanding of AIM2 biology and its functions in health and disease.

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Cell-autonomous epithelial activation of AIM2 (absent in melanoma-2) inflammasome by cytoplasmic DNA accumulations in primary Sjögren's syndrome

Cited by 33 publications

References 51 publications

Epithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis

Epithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis

AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases

AIM2 in health and disease: Inflammasome and beyond

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