CHARACTERIZATION OF THE ROLE OF CYTOKINE IL-15 IN OBESITY IN A MUrine MODEL

• Grant number: 25/04042-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alessandro dos Santos Farias
• Grantee: Matheus Frediani Cavicchioli Cruz
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

Obesity is a disease characterized by dysfunctions in multiple organ systems, such as the endocrine, cardiovascular and respiratory systems, and a series of comorbidities, such as diabetes, atherosclerosis and asthma. An important component of this disease is the occurrence of a chronic low-intensity inflammatory state, characterized by a sustained and sensitive, but significant increase in the levels of inflammatory mediators, including cytokines and acute phase proteins. The cytokine IL-15 belongs to the family of cytokines that bind to the ¿ chain receptor (CD132), such as IL-2, IL-7, IL-9 and IL-21. IL-15 is expressed primarily by dendritic cells, monocytes, and macrophages-collectively called antigen-presenting cells-while the ¿ subunit of the IL-15 receptor (IL15R¿), which forms the heterodimeric receptor IL15R together with CD132, is expressed by T and NK lymphocytes, besides antigen-presenting cells. The roles of IL-15 are related to IL-2, and include the proliferation and activation of CD8+ T and NK cells, thus having a role in the activation of cells with a cytotoxic profile. In CD4+ T cells, IL-15 promotes the induction of STAT5 phosphorylation and the differentiation of the regulatory T cell (Treg) profile, being important for the control of inflammation dependent on Th1 and Th17 cells, as demonstrated in the absence of this cytokine in inflammatory bowel disease. However, at low concentrations, this cytokine appears to promote the proliferation of conventional CD4+ T cells, even in the presence of Treg cells. In obesity, specifically, evidence seems to indicate that IL-15 has beneficial roles in metabolism at the adipose tissue level. Furthermore, in humans, serum levels of IL-15 are normally inversely related to adiposity. It is necessary, however, to understand the immune mechanisms by which this cytokine acts in the context of obesity, especially in CD4+ T cells, which are related to the development of the disease.