The Inflammasomes in Autoinflammatory Diseases with Skin Involvement

Abstract

During the past years, significant progress in the understanding of the complexity, regulation, and relevance of innate immune responses underlying several inflammatory conditions with neutrophilic skin involvement has been made. These diseases belong to the novel class of autoinflammatory diseases, and several are caused by mutations in genes regulating the function of innate immune complexes, termed inflammasomes, leading to enhanced secretion of the proinflammatory cytokine IL-1β. Consequently, targeting of IL-1β has proven successful in the treatment of these diseases, and the identification of related pathogenic mechanisms in other more common skin diseases characterized by autoinflammation and neutrophilic tissue damage also provides extended opportunities for therapy by interfering with IL-1 signaling.

Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming‐associated molecules (TLR2, TLR4, Dectin‐1, Dectin‐2 and NFκB) in Malassezia folliculitis

“…Inflammasomes are key components of the innate immunity for inflammation responses. Inflammasomes are generally characterised in professional immune cells, but keratinocytes can express at least NLRP1, NLRP3 and AIM2 inflammasomes . Our immunohistochemical results corroborate the constitutive expression of NLRP1, NLRP3, NLRC4, AIM2 inflammasomes in the normal human epidermis and pilosebaceous glands.…”

Function and regulation of IL‐1α in inflammatory diseases and cancer

“…IL‐1α and IL‐1β can have complimentary or contrasting functions in different types of cancers. Expression of both IL‐1α and IL‐1β is increased during genotoxic stress, and their secretion by necrosis or pyroptosis promotes the expression of vascular endothelial growth factor (VEGF) in the tumor tissue . 3‐Methylcholanthrene (MCA) induced fibrosarcoma development requires IL‐1β, but not IL‐1α expression in the host .…”

Severe Sweet's Syndrome with Elevated Cutaneous Interleukin-1β after Azathioprine Exposure: Case Report and Review of the Literature

“…Genetic mutations affecting proteins of the inflammasome complex or proteins that regulate the function of the inflammasome have been found in several of the autoinflammatory syndromes. Inflammasomes are a group of protein complexes that recognize a diverse set of pathogen- and/or danger-associated inflammation-inducing stimuli and that control the production of important proinflammatory cytokines such as IL-1β and IL-18 [26]. Mutations in inflammasome components may result in overactivity of the inflammasome or failure to limit IL-1-mediated inflammation, as is the case in CAPS such as Muckle-Wells syndrome that are due to activating mutations of the inflammasome component NLRP3.…”