Effects of oral Butyrate treatment in the relapse phase of experimental Psoriasis: focus on IL-17-producing lymphoid cells

• Grant number: 22/16236-2
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2023
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Hosana Gomes Rodrigues
• Grantee: Hosana Gomes Rodrigues
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• City of the host institution: Limeira
• Associated researchers: Marco Aurélio Ramirez Vinolo

Abstract

The unregulated activation of the immune system contributes to the development of psoriasis, a chronic relapsing-remitting disease that affects approximately 1.5% of the Brazilian population. Patients with psoriasis have periods of remission of the disease and later, during relapses, the lesions reappear in previously affected sites. T lymphocytes are identified as key cells for the reactivation of psoriasis due to the continuous release of IL-17, contributing to the thickening of the epidermis. Short-chain fatty acids have been studied as immunomodulatory nutrients that can act in the articulation of the immune response. However, the effects of oral administration of butyrate on the recurrence phase of psoriasis are still unknown. Thus, the objective of this study is to investigate the effects of oral administration of butyrate in the relapse phase of psoriasis, focusing on the action on IL-17-producing lymphoid cells. We hypothesize that butyrate will reduce the activation of IL-17-producing lymphoid cells, thereby inhibiting psoriasis relapse. For this, topical application of imiquimod (IMQ) will take place in two cycles to mimic chronic psoriatic inflammation. The first cycle will last for six days. The treatment with butyrate will start on the 7th day and continue until the 28th day. The second IMQ application cycle will take place between the 21st and 28th day of the protocol. To assess the involvement of membrane receptors in butyrate effects, we will perform key experiments with GPR43 and GPR109A knockout animals. We will also use the model of tributyrin administration and diet modification (rich in inulin) to confirm the effects of butyrate. Skin samples will be collected on the 28th day after starting the protocol. We will evaluate the effects of butyrate supplementation on macroscopic and microscopic aspects of the skin, as well as cell populations and cytokine gene expression by flow cytometry and RT-qPCR, respectively. The lipid composition of the skin and serum will be evaluated by gas chromatography coupled to mass spectrometry. In immunophenotyping assays we will identify the main IL-17 producing cell populations during the disease recurrence phase. Thus, we hope to be able to indicate new molecular targets to prevent psoriasis recurrence. (AU)