Role of Pink1-Mediated Mythophagy in Keratinocytes in the Development of Inflammation in Experimental Psoriasis Model

• Grant number: 22/13122-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Anthony Gabry da Silveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM
• Associated scholarship(s): 23/07057-0 - IL-17A induced mitophagy on mouse keratinocytes: a role for the inflammation-metabolism axis in psoriasis, BE.EP.IC

Abstract

Psoriasis is an autoimmune disease characterized by hyperproliferation of keratinocytes which also promote chronic inflammation in the skin. Furthermore, the inflammatory process is triggered by coordinated action of infiltrating immune cells in the skin and keratinocytes, where the latter release exacerbated levels of antimicrobial peptides, cytokines and chemokines. It is suggested that during activation of this cell, mitochondria act as an axis that will mediatereprogramming of the metabolic profile and phenotype fixation as observed in immune cells.Moreover, it has been shown that in psoriatic plaques there is an exacerbated production ofreactive oxygen species (ROS). This requires an apparatus of mechanisms that will preventoxidative stress, such as mitophagy mediated by PTEN-induced kinase 1 (Pink1), an autophagyprocess to clear dysfunctional mitochondrial compartments or the entire organelle. Despite itsprominence, this process is poorly studied in the context of psoriasis. Thus, in this project, we seek to test the hypothesis that the accumulation of dysfunctional mitochondria due to Pink1 absence promotes enhanced inflammation in models of experimental psoriasis. Experimental psoriasis will be induced by the topical application of imiquimod to Pink1 KO and Wild Type mice, divided into psoriatic and control groups. After that, all groups will have the epidermis of the ear extracted and used to analyze the impact of Pink1 absence in this inflammatory process, focusing on histopathological, metabolic and phenotypic changes. A better understanding of the role of Pink1 may indicate new therapeutic targets for psoriasis that may change the course of thedisease.