Abstract
Psoriasis is a chronic and recurrent inflammatory skin disease characterized by abnormal proliferation and differentiation of keratinocytes and activation of immune cells. However, the molecular driver that triggers this immune response in psoriatic skin remains unclear. The inflammation-related gene absent in melanoma 2 (AIM2) was identified as a susceptibility gene/locus associated with psoriasis. In this study, we investigated the role of AIM2 in the pathophysiology of psoriasis. We found elevated levels of mitochondrial DNA in patients with psoriasis, along with high expression of AIM2 in both the human psoriatic epidermis and a mouse model of psoriasis induced by topical imiquimod (IMQ) application. Genetic ablation of AIM2 reduced the development of IMQ-induced psoriasis by decreasing the production of type 3 cytokines (such as IL-17A and IL-23) and infiltration of immune cells into the inflammatory site. Furthermore, we demonstrate that IL-17A induced AIM2 expression in keratinocytes. Finally, the genetic absence of inflammasome components downstream AIM2, ASC, and caspase-1 alleviated IMQ-induced skin inflammation. Collectively, our data show that AIM2 is involved in developing psoriasis through its canonical activation.
Authors
Timna Varela Martins, Bruno Marcel Silva de Melo, Juliana Escher Toller-Kawahisa, Gabriel Victor Lucena da Silva, Conceição Elidianne Aníbal Silva, Isadora Marques Paiva, Gabriel Azevedo Públio, Marcos Henrique Rosa, Cacilda da Silva Souza, Dario Simões Zamboni, Fernando Q. Cunha, Thiago Mattar Cunha, Bernhard Ryffel, Nicolas Riteau, José C. Alves-Filho
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