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

Abstract

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.