The role of inflammasomes in cutaneous pathology

Abstract

Inflammasomes are large intracellular multiprotein complexes, which constitute a novel part of the innate immune system. In response to danger signals from pathogens or other harmful agents, inflammasomes assemble resulting in production of the inflammatory cytokines. We discuss recent knowledge of the role of deregulated inflammasome activity in skin pathologies such as autoinflammatory diseases as well as common skin diseases such as psoriasis and atopic dermatitis. We also present an insight into the activation and effector mechanisms of inflammasomes in skin carcinogenesis. The complex influence of inflammasome on cutaneous disorders raises new challenges and opportunities for the treatment of skin diseases.

Keywords: inflammasome; skin cancer; skin disease.

Figure 1

NLRP3 inflammasome assembly and activation. Upon activation, the NLRP3 protein interacts with adaptor protein ASC via the PYD domain and the CARD domain of ASC recruits the CARD domain of pro-caspase-1. The active complex of NLRP3–ASC–pro-caspase-1 is also named NLRP3 inflammasome. Finally, caspase-1 leads to activation via proteolytic cleavage of pro-IL-1β causing maturing of IL-1β NACHT – nucleotide-binding and oligomerization domain, CARD – caspase recruitment domain, LRR – leucine rich repeat domain, PYD – pyrin domain, NLRP3 – NOD-like receptor pyrin domain-containing protein 3.