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Inflammasomes in Common Immune-Related Skin Diseases.

ABSTRACT: The inflammasome is an important protein complex that cleaves the proinflammatory cytokines pro-IL-1? and pro-IL-18 into their active forms. Owing to its critical role in eliciting innate immune responses, IL-1? has been suggested to contribute to various skin diseases, including psoriasis, vitiligo, systemic lupus erythematosus (SLE), and atopic dermatitis (AD). Recently, several types of activators and inhibitors of different inflammasomes, as well as inflammasome-related genes and genetic susceptibility loci, have been identified in these immune-related common skin diseases. In particular, inflammasome activators and inhibitors presented highly cell-type-specific activity, suggesting that the inflammasome might perform different functions in different cell types. Moreover, most of these findings were based on experimental disease models, and the clinical features of the models partly resemble the typical symptoms of the diseases. In this review, from the perspective of activators and inhibitors, we collected evidence from the widely-studied inflammasomes, NLRP3, AIM2, and NLRP1, in psoriasis, vitiligo, SLE, and AD. Importantly, some small-molecule inhibitors hold therapeutic promise for the treatment of these diseases.

SUBMITTER: Tang L

PROVIDER: S-EPMC7247819 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Inflammasomes in Common Immune-Related Skin Diseases.

Tang Lili L Zhou Fusheng F

Frontiers in immunology 20200512

The inflammasome is an important protein complex that cleaves the proinflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms. Owing to its critical role in eliciting innate immune responses, IL-1β has been suggested to contribute to various skin diseases, including psoriasis, vitiligo, systemic lupus erythematosus (SLE), and atopic dermatitis (AD). Recently, several types of activators and inhibitors of different inflammasomes, as well as inflammasome-related genes and genetic sus ...[more]

PMID: 32528469

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Project description:BackgroundRecent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo.MethodsWe utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy.ResultsThe IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations.ConclusionThis study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

Dataset Information

Inflammasomes in Common Immune-Related Skin Diseases.

Publications

Inflammasomes in Common Immune-Related Skin Diseases.

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