Human keratinocytes express AIM2 and respond to dsDNA with IL-1β secretion

Kopfnagel, Verena; Wittmann, Miriam; Werfel, Thomas

doi:10.1111/j.1600-0625.2011.01382.x

Cited by 62 publications

(50 citation statements)

References 18 publications

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“…AIM2-mediated DNA sensing can trigger inflammasome activation, leading to the activation of caspase-1 and the catalytic cleavage of pro-forms of the pro-inflammatory cytokines IL-1β and IL-18 into their active secreted form. Given the observed high expression of the inflammasome protein AIM2 in skin, 22 we studied whether IL-1β −/− IL-18 −/− mice were able to mount similar CTL responses as WT mice. We found that intradermal electroporation induced similar specific CTL responses between the KO and WT mice measured as IFN-γ producingCTLs (Fig.…”

Section: Nf-κb Activation During Intradermal Dna Vaccination Is Essenmentioning

confidence: 99%

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Ligtenberg

Rojas-Colonelli

Kiessling

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Nf-κb Activation During Intradermal Dna Vaccination Is Essenmentioning

confidence: 99%

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Ligtenberg

Rojas-Colonelli

Kiessling

et al. 2013

Human Vaccines & Immunotherapeutics

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“…The remarkable increase of AIM2 expression in keratinocytes at site of acute and chronic skin barrier disruption-related inflammation, indicates a role for AIM2 inflammasome in both antimicrobial defense and also sustained chronic inflammation (de Koning et al, 2012). However, Kopfnagel and colleagues obtained contrasting results, suggesting that there is no intrinsic abnormality concerning the expression of AIM2 in keratinocytes of AD or psoriatic patients versus healthy controls, pointing out a general role of AIM2 in skin defense (Kopfnagel et al, 2011). Further investigations would be necessary to elucidate the contribution of AIM2 in inflammatory skin conditions.…”

Section: Aim2 In Autoimmunity and Skin Diseasesmentioning

confidence: 82%

The Duality of AIM2 Inflammasome: A Focus on its Role in Autoimmunity and Skin Diseases

Canavese¹

2016

American Journal of Pharmacology and Toxicology

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Understanding the inflammasome biology is one of the most exciting challenges in immuno-pharmacology. The role of the inflammasomes has been recognized in the host defense mechanism against invading pathogens and in the development of several conditions, such as cancer, auto-inflammatory, autoimmune, metabolic and neurodegenerative disorders. DNA recognition by the cells is a crucial immunological step leading to the initiation of an innate immune response. Absent in Melanoma 2 (AIM2) is a cytoplasmic sensor that perceives double-stranded DNA of microbial or host origin. Once the DNA is bound, AIM2 assembles a multiprotein complex named inflammasome, which drives pyroptosis and proteolytic cleavage of pro-IL-1β and pro-IL-18 pro-inflammatory cytokines, leading to a protective inflammasome-mediated host response. However, improper recognition of self-DNA by AIM2 triggers deleterious inflammatory responses, leading to systemic inflammation and several pathological conditions. Therefore, understanding the mechanisms of AIM2-inflammasome-mediated inflammation will provide an essential knowledge base to develop new successful therapeutic strategies to cure the outlined pathologies in which AIM2-inflammasome activation plays a key role, as well as to guide clinical practice. This mini-review provides an overview on the latest research findings on AIM2 inflammasome, with particular focus on its role in autoimmunity and skin disorders. An update on its therapeutic implications has also been documented.

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“…In the human gut, AIM2 is predominantly expressed in macrophages and epithelial cells throughout the small and large intestine [16][17][18]. AIM2 is best known as an intracellular danger sensor present in a number of tissues with strong immune regulation other than the gut, such as the lungs [19][20][21], joints [22,23], skin [24,25], liver [26][27][28], brain [29,30] and gingiva [31,32]. Furthermore, AIM2 has been associated with (auto-)…”

Section: Absent In Melanomamentioning

confidence: 99%

Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

Vanhove¹,

Peeters²,

Cleynen³

et al. 2017

Inflammasome

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epithelial cell proliferation, tight junction expression and the microbiome. Therefore, AIM2 plays a significant role in maintaining intestinal homeostasis. This review focuses on the multifunctional role of AIM2 in intestinal homeostasis by regulating intestinal immunity and preventing colorectal cancer development.Keywords: Inflammasome, Inflammatory Bowel Disease, Colorectal Cancer, Proliferation, Antimicrobial Peptides, Intestinal Microbiota, Tight Junctions 1 Introduction Inflammasomes in intestinal homeostasisRegulation of normal intestinal mucosal function is essential for the host's survival. The continuous interaction between the xenogenous and microbial environment, and the gut's immune system demands optimal regulation. Impaired functioning may result in intestinal barrier dysfunction, dysbiosis, inflammation and carcinogenesis [1,2]. Inflammasomes are important immune regulators for intestinal homeostasis that allow recruitment and activation of the inflammatory caspase-1, upon stimulation by a wide variety of triggers. This will activate downstream mediators, including interleukin-1β (IL-1β) and interleukin-18 (IL-18), that, in combination with other alarm molecules (eg. high mobility group box 1, HMGB1) are the driving force of inflammation [3]. Furthermore, activated caspase-1 can also trigger pyroptosis, a specific form of cell death associated with inflammation. In contrast to apoptosis, pyroptosis will release cytoplasmic components into the extracellular space that can fuel inflammatory processes in adjacent cells [4][5][6]. This distinction is important as apoptosis is characterized by chromatin condensation, cell vacuolization and phagocytosis Abstract: The intestinal mucosa is a difficult environment to maintain homeostasis as it is constantly challenged by microbial and food antigens. Maintaining an intact epithelial barrier, a continuous turnover of intestinal epithelial cells and normobiosis of the gut microbiota are essential components to prevent intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Inflammasomes are critical immune regulators that are involved in all of these processes. They are multiprotein complexes able to assemble upon interaction with a noxious stimulus that will subsequently lead to caspase-1 activation. Activated caspase-1 will orchestrate the maturation and release of proinflammatory cytokines IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. Both cytokine release and pyroptosis are initiated after detection of molecular patterns by a distinct inflammasome sensor protein. Absent in melanoma 2 (AIM2) is such an inflammasome sensor that specifically responds to the presence of double stranded DNA (dsDNA) in the cytoplasm, leading to the recruitment and activation of caspase-1. Recent studies revealed additional roles of AIM2 in controlling Review ArticleOpen Access

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Human keratinocytes express AIM2 and respond to dsDNA with IL-1β secretion

Cited by 62 publications

References 18 publications

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

The Duality of AIM2 Inflammasome: A Focus on its Role in Autoimmunity and Skin Diseases

Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

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