Lichen planus: altered
            <scp>AIM</scp>
            2 and
            <scp>NLRP</scp>
            1 expression in skin lesions and defective activation in peripheral blood mononuclear cells

Domingues, Rosana; Pietrobon, Anna Julia; Carvalho, Gabriel Costa de; Pereira, Newton Lindolfo; Sotto, Mírian Nacagami; Aoki, Valéria; Duarte, Alberto José da Silva; Sato, Maria Notomi

doi:10.1111/ced.13859

Cited by 5 publications

(7 citation statements)

References 18 publications

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“…Furthermore, activated Caspase 1 cleaves Gasdermin D which executes pyroptosis via pore formation in affected cell membranes ( 61 ). AIM2 is upregulated in skin samples of lichen planus patients ( 62 ). Inflammasome activity is enhanced in lupus erythematosus ( 63 ) and the inflammasome-activated cytokine IL18 is highly upregulated in the epidermis of CLE patients ( 64 ).…”

Section: Interface Dermatitis—the Pathogenic Backgroundmentioning

confidence: 99%

Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model

et al. 2021

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Interface dermatitis is a histopathological pattern mirroring a distinct cytotoxic immune response shared by a number of clinically diverse inflammatory skin diseases amongst which lichen planus and cutaneous lupus erythematosus are considered prototypic. Interface dermatitis is characterized by pronounced cytotoxic immune cell infiltration and necroptotic keratinocytes at the dermoepidermal junction. The initial inflammatory reaction is established by cytotoxic immune cells that express CXC chemokine receptor 3 and lesional keratinocytes that produce corresponding ligands, CXC motif ligands 9/10/11, recruiting the effector cells to the site of inflammation. During the resulting anti-epithelial attack, endogenous immune complexes and nucleic acids are released from perishing keratinocytes, which are then perceived by the innate immune system as danger signals. Keratinocytes express a distinct signature of pattern recognition receptors and binding of endogenous nucleic acid motifs to these receptors results in interferon-mediated immune responses and further enhancement of CXC chemokine receptor 3 ligand production. In this perspective article, we will discuss the role of innate nucleic acid sensing as a common mechanism in the perpetuation of clinically heterogeneous diseases featuring interface dermatitis based on own data and a review of the literature. Furthermore, we will introduce a keratinocyte-specific in vitro model of interface dermatitis as follows: Stimulation of human keratinocytes with endogenous nucleic acids alone and in combination with interferon gamma leads to pronounced production of distinct cytokines, which are essential in the pathogenesis of interface dermatitis. This experimental approach bears the capability to investigate potential therapeutics in this group of diseases with unmet medical need.

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Section: Interface Dermatitis—the Pathogenic Backgroundmentioning

confidence: 99%

Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model

et al. 2021

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Section: Role Of Inflammasomes In Autoimmune Skin Diseasesmentioning

confidence: 99%

“…In lesional skin of LP patients, IL–1β, AIM2 and NLRP1 protein were found to be highly expressed compared to skin of healthy controls ( 121 ). AIM2 protein was expressed both in the dermis and epidermis whereas NLRP1 and IL-1β were only found significantly increased in the dermis in skin lesions of LP patients ( 121 ). LP skin lesion samples showed higher AIM2 ( 121 ) and NLRP3 ( 122 ) transcript levels whereas NLRP1 transcript levels were similar compared to healthy controls ( 121 ).…”

Section: Role Of Inflammasomes In Autoimmune Skin Diseasesmentioning

confidence: 99%

“…AIM2 protein was expressed both in the dermis and epidermis whereas NLRP1 and IL-1β were only found significantly increased in the dermis in skin lesions of LP patients ( 121 ). LP skin lesion samples showed higher AIM2 ( 121 ) and NLRP3 ( 122 ) transcript levels whereas NLRP1 transcript levels were similar compared to healthy controls ( 121 ). Interestingly, in the same study, IL1B mRNA expression was found to be significantly downregulated in LP skin lesions compared to healthy controls ( 121 ), which may be due to a regulatory feedback mechanism leading to reduced inflammasome priming.…”

Section: Role Of Inflammasomes In Autoimmune Skin Diseasesmentioning

confidence: 99%

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Aberrant inflammasome activation as a driving force of human autoimmune skin disease

et al. 2023

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Autoimmune skin diseases are understood as conditions in which the adaptive immune system with autoantigen-specific T cells and autoantibody-producing B cells reacting against self-tissues plays a crucial pathogenic role. However, there is increasing evidence that inflammasomes, which are large multiprotein complexes that were first described 20 years ago, contribute to autoimmune disease progression. The inflammasome and its contribution to the bioactivation of interleukins IL-1β and IL-18 play an essential role in combating foreign pathogens or tissue damage, but may also act as a pathogenic driver of myriad chronic inflammatory diseases when dysfunctionally regulated. Inflammasomes containing the NOD-like receptor family members NLRP1 and NLRP3 as well as the AIM2-like receptor family member AIM2 have been increasingly investigated in inflammatory skin conditions. In addition to autoinflammatory diseases, which are often associated with skin involvement, the aberrant activation of the inflammasome has also been implied in autoimmune diseases that can either affect the skin besides other organs such as systemic lupus erythematosus and systemic sclerosis or are isolated to the skin in humans. The latter include, among others, the T-cell mediated disorders vitiligo, alopecia areata, lichen planus and cutaneous lupus erythematosus as well as the autoantibody-driven blistering skin disease bullous pemphigoid. Some diseases are characterized by both autoinflammatory and autoimmune responses such as the chronic inflammatory skin disease psoriasis. Further insights into inflammasome dysregulation and associated pathways as well as their role in forming adaptive immune responses in human autoimmune skin pathology could potentially offer a new field of therapeutic options in the future.

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“…CARD18 inhibits caspase-1, preventing pyroptosis and indirectly suppressing the secretion of IL-1β [ 41 , 291 ]. The inflammasome nucleating proteins AIM2 and NLRP1 were also up-regulated in CLP in the epidermis and dermis, respectively [ 292 ], again suggesting a potential role for inflammasomes and pyroptosis in enhancing inflammation in LP.…”

Section: Cell Death In Human Skin Diseasementioning

confidence: 99%

Cell death in skin function, inflammation, and disease

Anderton

Alqudah

2022

Biochemical Journal

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Cell death is an essential process that plays a vital role in restoring and maintaining skin homeostasis. It supports recovery from acute injury and infection and regulates barrier function and immunity. Cell death can also provoke inflammatory responses. Loss of cell membrane integrity with lytic forms of cell death can incite inflammation due to the uncontrolled release of cell contents. Excessive or poorly regulated cell death is increasingly recognised as contributing to cutaneous inflammation. Therefore, drugs that inhibit cell death could be used therapeutically to treat certain inflammatory skin diseases. Programmes to develop such inhibitors are already underway. In this review, we outline the mechanisms of skin-associated cell death programmes; apoptosis, necroptosis, pyroptosis, NETosis, and the epidermal terminal differentiation programme, cornification. We discuss the evidence for their role in skin inflammation and disease and discuss therapeutic opportunities for targeting the cell death machinery.

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Lichen planus: altered AIM 2 and NLRP 1 expression in skin lesions and defective activation in peripheral blood mononuclear cells

Cited by 5 publications

References 18 publications

Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model

Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model

Aberrant inflammasome activation as a driving force of human autoimmune skin disease

Cell death in skin function, inflammation, and disease

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