IL-17A induced mitophagy on mouse keratinocytes: a role for the inflammation-metabolism axis in psoriasis

• Grant number: 23/07057-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: September 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Anthony Gabry da Silveira
• Supervisor: Valerie Horsley
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Yale University, United States
• Associated to the scholarship: 22/13122-6 - Role of Pink1-Mediated Mythophagy in Keratinocytes in the Development of Inflammation in Experimental Psoriasis Model, BP.IC

Abstract

Psoriasis is a chronic autoimmune disease characterized by inflammation of the skin resulting from hyperproliferation of keratinocytes. IL-17A is a cytokine that plays a critical role in the inflammatory loop mediated by keratinocytes. We aim to investigate whether IL-17A induces mitochondrial damage in keratinocytes and how mitochondrial quality control mechanisms, such as mitophagy, could compensate for this damage while maintaining mitochondrial function. Preliminary results from our project in Brazil suggest an increased expression of Pink1, a mitochondrial membrane depolarization-sensing protein, with IL-17A stimulus in keratinocytes. We also observed higher expression of mitofusin 2. We would like to further investigate the functionality of mitochondrial quality control mechanisms upon treatment with IL 17 in order to understand the role of mitochondria in the development of psoriasis. For this purpose, we will use primary cultures of mouse (C57BL/6) keratinocytes isolated from healthy and psoriatic animals and divide them into experimental groups according to the delivery of small interference RNA, silencing PINK1 and MFN 1/2 genes. Next, we will analyze mitochondrial morphology by confocal and electron microscopy, and evaluate the expression of markers of mitophagy and psoriatic inflammation by immunoblotting. This study's aim is to identify new therapeutic strategies for psoriasis by revealing the functional mechanisms of mitochondrial quality control in keratinocytes, potentially leading to the restoration of mitochondrial function and reduction of skin inflammation. (AU)