Contribution of gamma delta T lymphocytes involved in pulmonary neutrophilia induced by ketogenic diet.

• Grant number: 24/10030-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date until: January 01, 2025
• End date until: July 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Amanda Valeria Cardoso Prestes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

Dietary interventions for the prevention, control, and treatment of disease represent approaches widely employed across the population. However, little is known about the immunological safety of these dietary changes for the individual. In particular, the consumption of ketogenic diets has been used for more than a century by different populations to control diseases such as diabetes, obesity and, more recently, refractory childhood epilepsy. Ketogenic diets are predominantly composed of lipids and a low level of proteins and carbohydrates and, therefore, are also known as "low carb" diets. How it has a low carbohydrate content, the body will find other ways to produce energy, in this case, lipids. This way of obtaining energy generates so-called ketone bodies, which give the diet name. Although their medicinal properties, ketogenic diets have recently started to be used indiscriminately and in an unsupervised manner by individuals who intend to lose weight quickly. Little is known about the consequences of this type of drastic diet change for healthy individuals. In this context, results obtained by the Mucosal Immunology Laboratory at ICBUSP showed that mice treated with the ketogenic diet exhibited a marked increase in a neutrophilic infiltrate in the lungs, which was accompanied by an increase in the number and frequency of T³´ lymphocytes capable of secreting IL-17. Neutrophil recruitment was dependent on IL-6 production and IL-17 receptor expression. This diet-induced change in the immune tone of the lung mucosa has led to an increase in susceptibility to inflammatory lung diseases such as COVID-19 and asthma. However, we still don't understand the mechanisms involved in this phenomenon. Therefore, the objective of this project is to evaluate the contribution of T³´ cells to neutrophilic lung inflammation induced by the ketogenic diet. The results obtained in this project will allow us to better understand the mechanisms involved in the communication axes between the intestinal and pulmonary mucosa, as well as the importance of studying the immunological safety of dietary changes in healthy individuals.