Effects of oral butyrate treatment on crosstalk between memory resident T cells and dendritic cells during experimental psoriasis.

• Grant number: 22/05395-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Hosana Gomes Rodrigues
• Grantee: Roberta Nicolli Sagiorato
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated scholarship(s): 25/01194-0 - Exploring the interplay between GLP-1 and short-chain fatty acids in modulating immune responses in skin, BE.EP.DR

Abstract

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. The development of psoriasis is the result of gene-environment interaction and is due to stressor triggers that drive the activation of dendritic cells that migrate to lymph nodes and secrete cytokines to activate T cells. Patients with psoriasis have periods of disease remission and, later, during relapses, the lesions reappear in previously affected sites, indicating the permanence of T lymphocytes in the skin that respond quickly to a new stimulus. Memory-resident T lymphocytes are identified as key cells for the reactivation of psoriasis due to the continuous release of inflammatory cytokines, contributing to the thickening of the epidermis. Short-chain fatty acids have been studied as immunomodulatory nutrients that can act in the immune response articulation. However, it is not yet known about the effects of oral administration of butyrate in reducing the activation of memory-resident T cells by dendritic cells (DCs). Thus, the objective of this work is to investigate the effects of oral administration of butyrate on experimental psoriasis in mice, focusing on the communication between memory-resident T cells and dendritic cells. Our hypothesis is that butyrate will reduce the activation of memory-resident T cells via dendritic cells. For this, the topical application of imiquimod will take place in two cycles to mimic chronic psoriatic inflammation. The first cycle will last six days. The butyrate treatment will take place from the 7th day and will continue until the end of the protocol. From the 21st day of the protocol, we will resume the topical application of imiquimod together with the butyrate treatment. Skin samples will be collected on the 24th day after starting the protocol. We will evaluate the effects of butyrate supplementation on the 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. After identification and isolation of memory resident T cell subpopulations, we will evaluate the effects of fatty acid butyrate on reducing T cell activation from dendritic cells by co-culture and butyrate treatment. The essentiality of dendritic cells for activation of memory resident T cells will be investigated by diphtheria toxin dependent depletion. Skin RNA sequencing and genomic DNA sequencing will be used to assess the effects of butyrate on global gene expression of psoriatic skin and to assess the effects of butyrate on skin microbiota composition, respectively.